Dose rate effectiveness in radiation-induced teratogenesis in mice

International Nuclear Information System (INIS)

Kato, F.; Ootsuyama, A.; Norimura, T.

2000-01-01

To investigate the role of p53 gene in tissue repair of teratogenic injury, we compared incidence of radiation-induced malformations in homozygous p53(-/-) mice, heterozygous p53(+/-) mice and wild-type p53(+/+) mice. After X-irradiation with 2 Gy at high dose rate on 9.5 days of gestation, p53(-/-) mice showed higher incidences of anomalies and higher resistance to prenatal deaths than p53(+/+) mice. This reciprocal relationship of radiosensitivity to anomalies and deaths supports the notion that embryos or fetuses have a p53-dependent 'guardian' that aborts cells bearing radiation-induced teratogenic DNA damage. In fact, after X-irradiation, the number of apoptotic cells was greatly increased in p53(+/+) fetuses but not in p53(-/-) fetuses. The same dose of γ-ray exposure at low dose rate on 9.5-10.5 day of gestation produced significant reduction of radiation-induced malformation in p53(+/+) and p53(+/-) mice, remained teratogenic for p53(-/-) mice. These results suggest that complete elimination of teratogenic damage from irradiated tissues requires the concerted cooperation of two mechanisms; proficient DNA repair and the p53-dependent apoptotic tissue repair. When concerted DNA repair and apoptosis functions efficiently, there is a threshold dose-rate for radiation-induced malformations. (author)

Carcinogenesis induced by low-dose radiation

Directory of Open Access Journals (Sweden)

Piotrowski Igor

2017-11-01

Full Text Available Although the effects of high dose radiation on human cells and tissues are relatively well defined, there is no consensus regarding the effects of low and very low radiation doses on the organism. Ionizing radiation has been shown to induce gene mutations and chromosome aberrations which are known to be involved in the process of carcinogenesis. The induction of secondary cancers is a challenging long-term side effect in oncologic patients treated with radiation. Medical sources of radiation like intensity modulated radiotherapy used in cancer treatment and computed tomography used in diagnostics, deliver very low doses of radiation to large volumes of healthy tissue, which might contribute to increased cancer rates in long surviving patients and in the general population. Research shows that because of the phenomena characteristic for low dose radiation the risk of cancer induction from exposure of healthy tissues to low dose radiation can be greater than the risk calculated from linear no-threshold model. Epidemiological data collected from radiation workers and atomic bomb survivors confirms that exposure to low dose radiation can contribute to increased cancer risk and also that the risk might correlate with the age at exposure.

Studies on adaptive response of lymphocyte transformation induced by low-dose irradiation

International Nuclear Information System (INIS)

Du Zeji; Su Liaoyuan; Tian Hailin; Zou Huawei

1995-10-01

Human peripheral blood lymphocytes stimulated by mitogen in vitro for 24 h were exposed to low-dose γ-ray irradiation (0.5∼4.0 cGy, adaptive dose). They showed an adaptive response to the inhibition of 3 H-TdR incorporation by subsequent higher acute doses of γ-ray (challenge dose). At the interval of 24 h between adaptive dose and challenge dose, the strongest adaptive response induced by low-dose irradiation was found. It is also found that the response induced by 1.0 cGy of adaptive dose was more obvious than that by other doses and that 3.0 Gy of challenge dose produced the strongest adaptive response. As the challenge doses increased, the adaptive response reduced. (2 figs., 2 tabs.)

A physiologically based biodynamic (PBBD) model for estragole DNA binding in rat liver based on in vitro kinetic data and estragole DNA adduct formation in primary hepatocytes

NARCIS (Netherlands)

Paini, A.; Punt, A.; Viton, F.; Scholz, G.; Delatour, T.; Marin-Kuan, M.; Schilter, B.; Bladeren, van P.J.; Rietjens, I.

2010-01-01

Estragole has been shown to be hepatocarcinogenic in rodent species at high-dose levels. Translation of these results into the likelihood of formation of DNA adducts, mutation, and ultimately cancer upon more realistic low-dose exposures remains a challenge. Recently we have developed

Estimation of the Radon-induced Dose for Russia's Population: Methods and Results

International Nuclear Information System (INIS)

Marenny, A.M.; Savkin, M.N.; Shinkarev, S.M.

2000-01-01

A model is proposed for inferring the radon-induced annual average collective and personal doses, as well as the dose distribution of the population, all over Russia from selective radon monitoring in some regions of Russia. The model assumptions and the selective radon monitoring results that underlie the numerical estimates obtained for different population groups are presented. The current estimate of the collective radon-induced dose received by the population of Russia (148,100,000 as of 1996) is about 130,000 man Sv, of which 55,000 man Sv is for the rural population (27% of the total population) and 75,000 man Sv for the urban population (73% of the total). The average radon-induced personal dose in Russia is estimated to be about 0.87 mSv. About 1,000,000 people receive annual doses above 10 mSv, including some 200,000 people who receive doses above 20 mSv annually. The ways of making the current estimates more accurate are outlined. (author)

Effect and adaptive response of lymphocytes DNA induced by low dose irradiation

International Nuclear Information System (INIS)

Du Zeji; Su Liaoyuan; Tian Hailin

1994-09-01

Fluorometric analysis of DNA unwinding (FADU) was conducted and was proved to be an optimal method for studying DNA strand breaks induced by low dose irradiation. The linear dose response curve was obtained. The minimum detected dose was 0.3 Gy. There was no effect of low dose γ-rays (0.5∼8.0 cGy) on DNA strand breaks of quiescent and mitogen-induced lymphocytes. The 0.5∼4.0 cGy γ-rats could induce adaptive response of lymphocytes' DNA strand breaks, especially, at the doses of 2.0 and 4.0 cGy. The challenge doses of 5∼20 Gy could make the adaptive response appearance, and the 15 Gy was the best one. The 3-AB could powerfully inhibit the adaptive response. The repair of DNA strand breaks (37 degree C, 15∼60 min) caused by 15 Gy γ-rays could be promoted by the low dose γ-ray irradiation (2.0 cGy), but no difference was found at 37 degree C, 120 min

Potency of carcinogens derived from covalent DNA binding and stimulation of DNA synthesis in rat liver

International Nuclear Information System (INIS)

Lutz, W.K.; Buesser, M.T.; Sagelsdorff, P.

1984-01-01

In order to investigate the role of the stimulation of cell division for the initiation (and possibly promotion) of liver tumors by chemical carcinogens, the incorporation of radiolabelled thymidine into liver DNA was determined in male rats. Single doses of various levels of aflatoxin B1, benzidine and carbon tetrachloride (all known to be genotoxic via DNA binding) did not affect cell division, whereas several hepatocarcinogens known not to bind to DNA (alpha-HCH, clofibrate, and 2,3,7,8-tetrachlorodibenzo-p-dioxin) gave rise to a dose-dependent stimulation of liver DNA synthesis within 24 h. An equation combining the influences of mitotic stimulation, expressed as dose required to double the control level of DNA synthesis, and DNA binding potency, expressed as the Covalent Binding Index, correlated well with the carcinogenic potency for both classes of hepatocarcinogens

Very low dose and dose-rate X-ray induced adaptive response in human lymphocytes at various cell cycle stages against bleomycin induced chromatid aberrations

International Nuclear Information System (INIS)

Hossein Mozdarani; Moghadam, R.N.

2007-01-01

Complete text of publication follows. Objective: To study the adaptive response induced by very low doses of X-rays at very low dose rate in human lymphocytes at different cell cycle stages followed by a challenge dose of bleomycin sulphate at G2 phase. Materials and Methods: Human peripheral blood lymphocytes before (G0) and after PHA stimulation (G1 and G2) were exposed to 1 and 5 cGy X-rays generated by a fluoroscopy unit with a dose rate of 5.56 mGy/min and challenged with 5 μg/ml bleomycin sulphate (BLM) 48 hours after culture initiation. Mitotic cells were arrested at metaphase by addition of colcemid in cultures 1.5 h before harvesting. Harvesting and slide preparation was performed using standard method. 100 well spread metaphases were analyzed for the presence of chromatid type aberrations for each sample. Results: Results obtained indicate that there is a linear relationship between the dose of BLM and chromatid aberrations below 5 μg/ml (R=0.93, p<0.0001). The results also show that pretreatment of lymphocytes with low dose X-rays at G0, G1 and G2 phases of the cell cycle significantly reduced the sensitivity of lymphocytes to the clastogenic effects of BLM in G2. Much lower frequencies of chromatid aberrations were observed in X-ray irradiated lymphocytes following BLM treatment (p<0.05). The magnitudes of adaptation induced at different phases of the cell cycle were not significantly different. Furthermore, there was no a significant difference in the magnitude of adaptive response induced by either 1 or 5 cGy X-rays. Conclusion: These observations might indicate that resistance of pre-exposure of lymphocytes to very low doses of X-rays protects them from clastogenic effects of BLM. This effect might be due to initial DNA damage induced in these cells leading to provocation of an active DNA repair mechanism independent of cell cycle stage.

Radiation-induced cell mutations as a function of dose rate

International Nuclear Information System (INIS)

Kiefer, J.

1987-01-01

A brief review of the data in the literature is presented and forms the background of the experimental data given by the author obtained with exponential long-term cultures of V79 hamster cells exposed over a period of up to 35 days to different dose rates of gamma radiation. The experimental results show that at a dose rate of 40 mGy/hour the number of induced mutations is reduced, - which is in agreement with literature data - , but a dose rate of less than 30 mGy/hour makes the induced mutations leap to a value clearly higher than those induced by acute irradiation. As in addition to the mutations recombination is a significant factor of the radiation risk, experiments with a heterozygotic yeast strain have been made, as there is to date no reliable mammalian cell system available for this kind of research. Long-term radiation exposure of the yeast cells over a period of six weeks drastically increased the rate of recombinations, to a value higher by a factor of about 4 than that induced by acute irradiation. (orig.) [de

Dose-effect relationship of apoptosis induced by fission-neutron in murine thymocytes

International Nuclear Information System (INIS)

Yuan Bin; Li Liang; Xue Wencheng; Sun Jianmin; Wang Baoqin

2000-01-01

Objective: To investigate the effectiveness of high LET fission-neutron to induce apoptosis in murine thymocytes and to compare it with that of low LET 60 Co γ-ray. Methods: Apoptosis induction was studied qualitatively by light and transmission electron microscopy and DNA gel electrophoresis,also quantitatively by flow cytometry(FCM) and diphenylamine (DPA)methods. Results: DNA ladders of murine thymocytes were detectable, the typical apoptosis of thymocytes could be observed morphologically by means of light and electron microscopy at 6 h after fission-neutron irradiation with doses ranging from 0.5 to 5.0 Gy, meanwhile the percentages of apoptosis increased with increasing doses. After exposure to γ-rays with doses ranging from 1.0 to 30 Gy, the experimental results were similar to those from neutron radiation. The incidence of apoptosis peaked at about 20 Gy, the percentages did not increase further when doses increased. Conclusion: Apoptosis of murine thymocytes can be induced when mice are exposed to either fission-neutron (0.5-5.0 Gy) or to γ-ray (1-30 Gy). Although the relationship between apoptosis and radiation doses is similar, the percentage of apoptosis induced by neutron irradiation is higher than that induced by γ-irradiation. The RBE values of fission-neutron for inducing apoptosis murine thymocytes are 2.09 (by FCM method) and 2.37 (by DPA method), respectively. These results also suggest that fission-neutron-induced murine immune tissue is more severe than that induced by γ-rays at several hours post-irradiation and this might be the basis for heavy damage to immune tissues induced by fission-neutron-irradiation in later period

Dose-response study of thimerosal-induced murine systemic autoimmunity

International Nuclear Information System (INIS)

Havarinasab, S.; Lambertsson, L.; Qvarnstroem, J.; Hultman, P.

2004-01-01

The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury. A.SW mice were exposed to 1.25-40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 μg Hg/kg bw and a concentration of 21 and 1.9 μg Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose-response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury

Mode of action analysis for the synthetic pyrethroid metofluthrin-induced rat liver tumors: evidence for hepatic CYP2B induction and hepatocyte proliferation.

Science.gov (United States)

Deguchi, Yoshihito; Yamada, Tomoya; Hirose, Yukihiro; Nagahori, Hirohisa; Kushida, Masahiko; Sumida, Kayo; Sukata, Tokuo; Tomigahara, Yoshitaka; Nishioka, Kazuhiko; Uwagawa, Satoshi; Kawamura, Satoshi; Okuno, Yasuyoshi

2009-03-01

Two-year treatment with high doses of Metofluthrin produced hepatocellular tumors in both sexes of Wistar rats. To understand the mode of action (MOA) by which the tumors are produced, a series of studies examined the effects of Metofluthrin on hepatic microsomal cytochrome P450 (CYP) content, hepatocellular proliferation, hepatic gap junctional intercellular communication (GJIC), oxidative stress and apoptosis was conducted after one or two weeks of treatment. The global gene expression profile indicated that most genes with upregulated expression with Metofluthrin were metabolic enzymes that were also upregulated with phenobarbital. Metofluthrin induced CYP2B and increased liver weights associated with centrilobular hepatocyte hypertrophy (increased smooth endoplasmic reticulum [SER]), and induction of increased hepatocellular DNA replication. CYP2B1 mRNA induction by Metofluthrin was not observed in CAR knockdown rat hepatocytes using the RNA interference technique, demonstrating that Metofluthrin induces CYP2B1 through CAR activation. Metofluthrin also suppressed hepatic GJIC and induced oxidative stress and increased antioxidant enzymes, but showed no alteration in apoptosis. The above parameters related to the key events in Metofluthrin-induced liver tumors were observed at or below tumorigenic dose levels. All of these effects were reversible upon cessation of treatment. Metofluthrin did not cause cytotoxicity or peroxisome proliferation. Thus, it is highly likely that the MOA for Metofluthrin-induced liver tumors in rats is through CYP induction and increased hepatocyte proliferation, similar to that seen for phenobarbital. Based on analysis with the International Life Sciences Institute/Risk Science Institute MOA framework, it is reasonable to conclude that Metofluthrin will not have any hepatocarcinogenic activity in humans, at least at expected levels of exposure.

Low-dose radiation-induced adaptive response in bone marrow cells of mice

International Nuclear Information System (INIS)

Farooqi, Zeba; Kesavan, P.C.

1993-01-01

Using bone marrow cells of whole body irradiated mice, the cytogenetic adaptive response induced by low conditioning doses of gamma-rays was investigated. The conditioning doses (0.025 and 0.05 Gy) were given at a dose-rate of 1.67 Gy/min. The challenging dose of 1 Gy was given at a dose-rate of 0.045 Gy/s. The challenging dose was given at different time intervals after the conditioning dose. The time intervals between the conditioning dose and challenging dose were 2, 7.5, 13, 18.5 and 24 h. When the time interval between the conditioning dose and the challenging dose was 2 h, both conditioning doses (0.025 and 0.05 Gy) reduced the frequency of MNPCEs and chromosomal aberrations in the bone marrow cells. The data collected at different time intervals (7.5, 13, 18.5 h) reveal that the radioadaptive response persisted for a longer time when the lower conditioning dose (0.025 Gy) was given. With the higher conditioning dose (0.05 Gy), the radioadaptive response disappeared after a time interval of 13 h. When the time interval between the conditioning dose and the challenging doses was 18.5 or 24 h, only the lower conditioning dose appeared effective in inducing the radioadaptive response

Cell proliferation studies in rodent hepatocytes during 1,4-dichlorobenzene administration

International Nuclear Information System (INIS)

Eldridge, S.R.; Tilbury, L.F.; Randall, H.; Goldsworthy, T.L.; Butterworth, B.E.

1990-01-01

In the NTP bioassay, 1,4-dichlorobenzene (DCB) induced hepatocellular carcinomas in mice, but not in rats. Because DCB is not DNA reactive, a cell proliferation study under conditions of the bioassay was undertaken to determine whether increased cell proliferation might play a role in DCB-induced hepatocarcinogenicity. DCB was administered in corn oil by gavage at the highest bioassay dose to male B6C3F1 mice (600 mg/kg) and male F344 rats (300 mg/kg) for five consecutive days. Cell proliferation was detected by labeling hepatocytes with either 5-bromo-2'-deoxyuridine (BRDU) or 3 H-thymidine delivered during the entire treatment period by subcutaneously implanted osmotic pumps. An increase in liver weight as a percentage of body weight was observed in treated mice (6.7±0.6 vs. 5.9±0.2) and rats (4.7±0.1 vs. 4.0±0.2) compared to controls. No significant elevations in plasma enzymes were found in either treated species, indicating a lack of overt hepatotoxicity. Histopathological evaluation revealed no evidence of hepatotoxicity in either species. The percentage of hepatocytes in S-phase was increased approximately 10-fold in both treated mice and rats compared to the respective control animals. Mice exhibited a centrilobular pattern of labeled hepatocytes, whereas rat hepatocytes were labeled hepatocytes, whereas rat hepatocytes were labeled throughout the lobules. These data demonstrate the hepatic mitogenic activity of DCB in mice and rats. However, this response dose not correlate with DCB-induced hepatocarcinogenicity. Further studies are required to examine the extent, duration and nature of the proliferative response in order to understand the species-specific effects of DCB

Low-Dose Radiation Induces Genes Promoting Cell Survival

International Nuclear Information System (INIS)

Liu, Shu-Zheng; Chen, Dong; Mu, Ying

1999-01-01

Apoptosis is an important process controlling homeostasis of the body. It is influenced by stimuli constantly arising from the external and internal environment of the organism. It is well known that radiation could induce apoptosis of cells in vitro and in vivo. However, the dose-effect relationship of apoptosis extending to the low-dose range has scarcely been studied. Here, the molecular basis of the phenomenon is explored by examining the changes in expression of some of the proapoptotic and antiapoptotic genes

Induction of somatic mutations by low-dose X-rays: the challenge in recognizing radiation-induced events.

Science.gov (United States)

Nagashima, Haruki; Shiraishi, Kumiko; Ohkawa, Saori; Sakamoto, Yuki; Komatsu, Kenshi; Matsuura, Shinya; Tachibana, Akira; Tauchi, Hiroshi

2017-10-19

It is difficult to distinguish radiation-induced events from spontaneous events during induction of stochastic effects, especially in the case of low-dose or low-dose-rate exposures. By using a hypersensitive system for detecting somatic mutations at the HPRT1 locus, we investigated the frequency and spectrum of mutations induced by low-dose X-rays. The mutant frequencies induced by doses of >0.15 Gy were statistically significant when compared with the spontaneous frequency, and a clear dose dependency was also observed for mutant frequencies at doses of >0.15 Gy. In contrast, mutant frequencies at doses of 0.2 Gy. Our observations suggest that there could be a critical dose for mutation induction at between 0.1 Gy and 0.2 Gy, where mutagenic events are induced by multiple DNA double-strand breaks (DSBs). These observations also suggest that low-dose radiation delivered at doses of <0.1 Gy may not result in DSB-induced mutations but may enhance spontaneous mutagenesis events. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

A blinded, randomized, controlled trial of three doses of high-dose insulin in poison-induced cardiogenic shock.

Science.gov (United States)

Cole, J B; Stellpflug, S J; Ellsworth, H; Anderson, C P; Adams, A B; Engebretsen, K M; Holger, J S

2013-05-01

High dose insulin (HDI) has proven superior to glucagon and catecholamines in the treatment of poison-induced cardiogenic shock (PICS) in previous animal studies. Standard recommendations for dosing of insulin vary and the optimal dose of HDI in PICS has not been established. Our hypothesis was a dose of 10 U/kg/hr of HDI would be superior to 1 U/kg/hr with cardiac output (CO) as our primary outcome measure in pigs with propranolol-induced PICS. This was a blinded, prospective, randomized trial with 4 arms consisting of 4 pigs in each arm. The arms were as follows: placebo (P), 1 U/kg/hr (HDI-1), 5 U/kg/hr (HDI-5), and 10 U/kg/hr (HDI-10). Cardiogenic shock was induced with a bolus of 0.5 mg/kg of propranolol followed by an infusion of 0.25 mg/kg/min until the point of toxicity, defined as 0.75 x (HR x MAP) was reached. At this point the propranolol infusion was decreased to 0.125 mg/kg/min and a 20 mL/kg bolus of normal saline (NS) was administered. The protocol was continued for 6 hours or until the animals died. 2 pigs died in the P arm, 1 pig died each in the HDI-1 and HDI-5 arms, and all pigs lived in the HDI-10 arm. There was a statistically significant difference in dose by time interaction on CO of 1.13 L/min over the 6 hr study period (p = < 0.001). There was also a statistically significant difference in dose by time interaction on MAP, HR, and systemic vascular resistance (SVR). No statistically significant difference was found between any of the arms regarding glucose utilization. HDI was statistically and clinically significantly superior to placebo in this propranolol model of PICS. Furthermore a dose response over time was found where CO increased corresponding to increases in doses of HDI.

Effect of low doses of cannabidiolic acid and ondansetron on LiCl-induced conditioned gaping (a model of nausea-induced behaviour) in rats.

Science.gov (United States)

Rock, E M; Parker, L A

2013-06-01

To determine the minimally effective dose of cannabidiolic acid (CBDA) that effectively reduces lithium chloride (LiCl)-induced conditioned gaping reactions (nausea-induced behaviour) in rats and to determine if these low systemic doses of CBDA (5-0.1 μg·kg⁻¹) relative to those of CBD could potentiate the anti-nausea effects of the classic 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, ondansetron (OND). We investigated the efficacy of low doses of CBDA to suppress acute nausea, assessed by the establishment of conditioned gaping to a LiCl-paired flavour in rats. The potential of threshold and subthreshold doses of CBDA to enhance the reduction of nausea-induced conditioned gaping by OND were then determined. CBDA (at doses as low as 0.5 μg·kg⁻¹) suppressed nausea-induced conditioned gaping to a flavour. A low dose of OND (1.0 μg·kg⁻¹) alone reduced nausea-induced conditioned gaping, but when it was combined with a subthreshold dose of CBDA (0.1 μg·kg⁻¹) there was an enhancement in the suppression of LiCl-induced conditioned gaping. CBDA potently reduced conditioned gaping in rats, even at low doses and enhanced the anti-nausea effect of a low dose of OND. These findings suggest that combining low doses of CBDA and OND will more effectively treat acute nausea in chemotherapy patients. © 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.

Okadaic acid for radiation dose estimation using drug-induced premature chromosome condensation

International Nuclear Information System (INIS)

Wang Chunyan; Zhang Wei; Su Xu

2005-01-01

Objective: To establish simple biological method for high irradiation dose estimation using drug-induced prematurely condensed chromosomes (PCC) aberrations. Methods: Peripheral blood was taken from healthy adults and irradiated by 0, 1, 2, 5, 10, 15, 20 and 25 Gy 60 Co γ-rays. Then the blood samples were cultured for 48 hrs. One hr before the end of culture , okadaic acid was added into culture medium to induce PCC rings, which were counted for each dose point. Results: The yield of PCC rings was increased with the dose of radiation until 20 Gy. Within the range of 1 to 20 Gy, there was a good dose-response relationship between the yield of PCC rings and radiation dose. Conclusion: Compared with the analysis of frequency of dicentrics, the yield of PCC rings could be a good biodosimetry indicator for estimation of high dose irradiation. (authors)

Search for the lowest irradiation dose from literatures on radiation-induced breast cancer

Energy Technology Data Exchange (ETDEWEB)

Yoshizawa, Y; Kusama, T [Tokyo Univ. (Japan). Faculty of Medicine

1975-12-01

A survey of past case reports concerning radiation-induced breast cancer was carried out in order to find the lowest irradiation dose. The search of literature published since 1951 revealed 10 cases of radiation-induced breast cancer. Only 5 cases had precise descriptions of the irradiation dose. The lowest irradiation dose was estimated at 1470 rads in the case of external X-ray irradiation for tuberous angioma. All of cases of radiation-induced breast cancer had received radiation for the treatment of nonmalignant tumors, such as pulmonary tuberculosis, mastitis, and tuberous angioma. There also were three statistical studies. The first concerned atomic bomb survivors, the second, pulmoanry tuberculous patients subjected to frequent fluoroscopies, and the third, patients of acute post partum mastitis. These statistical studies had revealed a significant increase in the incidence of breast cancer in the irradiated group, but there was little information about the lowest irradiation dose. It was noticed that radiation-induced breast cancer was more numerous in the upper inner quadrant of the breast. Most histopathological findings of radiation-induced breast cancer involved duct cell carcinoma. The latent period was about 15 years.

Low-Dose Adefovir-Induced Hypophosphatemic Osteomalacia on Whole-Body Bone Scintigraphy

Energy Technology Data Exchange (ETDEWEB)

Kim, Sung Hoon; Won, Kyoung Sook; Song, Bongil; Jo, Il; Zeon, Seok Kil [Keimyung Univ., Daegu (Korea, Republic of)

2013-12-15

While adefovir dipivoxil (ADV) effectively suppresses the hepatitis B virus, it can cause proximal renal tubular dysfunction leading to phosphate wasting. The safety of low-dose ADV (a dose of 10 mg/day), which does not induce clinically significant nephrotoxicity, is well recognized, but a few cases of hypophosphatemic osteomalacia (HO) caused by low-dose ADV therapy have recently been reported. Although HO induced by low-dose ADV therapy is rare, the presence of bone pain in patients treated with ADV should be monitored. Bone scintigraphy can be performed to confirm the occurrence of osteomalacia and to determine the disease extent. Bone scintigraphic and radiological image findings with a brief review of the literature are presented in this article. We report two cases of HO induced by low-dose ADV therapy that showed multifocal increased radiotracer uptakes in the bilateral bony ribs, spines, pelvic bones and lower extremities on whole-body bone scintigraphy. Bone pain gradually improved after phosphate supplementation and by changing the antiviral agent. Whole-body bone scintigraphy is a highly sensitive imaging tool and can show disease extent at once in the setting of the wide range of the clinical spectrum with nonspecific radiological findings. Furthermore, frequent involvement of the lower extremities, as a result of maximum weight bearing, could be an additional scintigraphic clue for the diagnosis of HO. These cases could be helpful for both clinicians prescribing ADV and nuclear physicians to prevent delayed diagnosis and plan further appropriate treatment.

Low-Dose Adefovir-Induced Hypophosphatemic Osteomalacia on Whole-Body Bone Scintigraphy

International Nuclear Information System (INIS)

Kim, Sung Hoon; Won, Kyoung Sook; Song, Bongil; Jo, Il; Zeon, Seok Kil

2013-01-01

While adefovir dipivoxil (ADV) effectively suppresses the hepatitis B virus, it can cause proximal renal tubular dysfunction leading to phosphate wasting. The safety of low-dose ADV (a dose of 10 mg/day), which does not induce clinically significant nephrotoxicity, is well recognized, but a few cases of hypophosphatemic osteomalacia (HO) caused by low-dose ADV therapy have recently been reported. Although HO induced by low-dose ADV therapy is rare, the presence of bone pain in patients treated with ADV should be monitored. Bone scintigraphy can be performed to confirm the occurrence of osteomalacia and to determine the disease extent. Bone scintigraphic and radiological image findings with a brief review of the literature are presented in this article. We report two cases of HO induced by low-dose ADV therapy that showed multifocal increased radiotracer uptakes in the bilateral bony ribs, spines, pelvic bones and lower extremities on whole-body bone scintigraphy. Bone pain gradually improved after phosphate supplementation and by changing the antiviral agent. Whole-body bone scintigraphy is a highly sensitive imaging tool and can show disease extent at once in the setting of the wide range of the clinical spectrum with nonspecific radiological findings. Furthermore, frequent involvement of the lower extremities, as a result of maximum weight bearing, could be an additional scintigraphic clue for the diagnosis of HO. These cases could be helpful for both clinicians prescribing ADV and nuclear physicians to prevent delayed diagnosis and plan further appropriate treatment

Influence of dosing times on cisplatin-induced peripheral neuropathy in rats

International Nuclear Information System (INIS)

Seto, Yoshihiro; Okazaki, Fumiyasu; Horikawa, Keiji; Zhang, Jing; Sasaki, Hitoshi; To, Hideto

2016-01-01

Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague–Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy. The online version of this article (doi:10.1186/s12885-016-2777-0) contains supplementary material, which is available to authorized users

Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B{sub 1}

Energy Technology Data Exchange (ETDEWEB)

Techapiesancharoenkij, Nirachara [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Fiala, Jeannette L.A. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Croy, Robert G.; Wogan, Gerald N. [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Groopman, John D. [Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (United States); Ruchirawat, Mathuros [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Bangkok 10210 (Thailand); Essigmann, John M., E-mail: jessig@mit.edu [Department of Biological Engineering and Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 (United States)

2015-01-01

Aflatoxin B{sub 1} (AFB{sub 1}) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB{sub 1}-DNA adducts in AFB{sub 1}-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB{sub 1} and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB{sub 1} administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB{sub 1}-induced hepatotoxicity. At 24 h after AFB{sub 1} administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB{sub 1}-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB{sub 1} hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer. - Highlights: • This study revealed sulforaphane (SF)-deregulated gene sets in aflatoxin B{sub 1} (AFB{sub 1})-treated rat livers. • SF redirects biochemical networks toward lipid biosynthesis in AFB{sub 1}-dosed rats. • SF enhanced gene sets that would be expected to favor cell repair and regeneration.

Radiation-induced attenuation in polarization maintaining fibers: low dose rate response, stress, and materials effects

International Nuclear Information System (INIS)

Gingerich, M.E.; Friebele, E.J.; Hickey, S.J.; Brambani, L.A.; Onstott, J.R.

1989-01-01

The loss induced in polarization-maintaining (PM) fibers by low dose rate <0.01 Gy/h, where 1 Gy = 100 rads(Si) radiation exposure has been found to vary from <0.4 to ∼6 dB/km-10 Gy, depending on the wavelength of measurement and the fiber. Correlations have been established between low dose rate response and the ''permanent'' induced loss determined by fitting the recovery of the induced loss following high dose rate exposure to nth-order kinetics. Using this technique, both 0.85- and 1.3-μm PM fibers have been found which show virtually no permanent incremental loss and would therefore appear to be resistant to low dose rate radiation environments. The asymmetric stress inherent in PM fibers has been shown to reduce the permanent induced loss, while the recovery of the radiation-induced attenuation was found to be enhanced in fibers with Ge-F-doped silica clads

Total dose induced latch in short channel NMOS/SOI transistors

International Nuclear Information System (INIS)

Ferlet-Cavrois, V.; Quoizola, S.; Musseau, O.; Flament, O.; Leray, J.L.; Pelloie, J.L.; Raynaud, C.; Faynot, O.

1998-01-01

A latch effect induced by total dose irradiation is observed in short channel SOI transistors. This effect appears on NMOS transistors with either a fully or a partially depleted structure. It is characterized by a hysteresis behavior of the Id-Vg characteristics at high drain bias for a given critical dose. Above this dose, the authors still observe a limited leakage current at low drain bias (0.1 V), but a high conduction current at high drain bias (2 V) as the transistor should be in the off-state. The critical dose above which the latch appears strongly depends on gate length, transistor structure (fully or partially depleted), buried oxide thickness and supply voltage. Two-dimensional (2D) numerical simulations indicate that the parasitic condition is due to the latch of the back gate transistor triggered by charge trapping in the buried oxide. To avoid the latch induced by the floating body effect, different techniques can be used: doping engineering, body contacts, etc. The study of the main parameters influencing the latch (gate length, supply voltage) shows that the scaling of technologies does not necessarily imply an increased latch sensitivity. Some technological parameters like the buried oxide hardness and thickness can be used to avoid latch, even at high cumulated dose, on highly integrated SOI technologies

Study on cellular survival adaptive response induced by low dose irradiation of 153Sm

International Nuclear Information System (INIS)

Zhu Shoupeng; Xiao Dong

1999-01-01

The present study engages in determining whether low dose irradiation of 153 Sm could cut down the responsiveness of cellular survival to subsequent high dose exposure of 153 Sm so as to make an inquiry into approach the protective action of adaptive response by second irradiation of 153 Sm. Experimental results indicate that for inductive low dose of radionuclide 153 Sm 3.7 kBq/ml irradiated beforehand to cells has obvious resistant effect in succession after high dose irradiation of 153 Sm 3.7 x 10 2 kBq/ml was observed. Cells exposed to low dose irradiation of 153 Sm become adapted and therefore the subsequent cellular survival rate induced by high dose of 153 Sm is sufficiently higher than high dose of 153 Sm merely. It is evident that cellular survival adaptive response could be induced by pure low dose irradiation of 153 Sm only

Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

International Nuclear Information System (INIS)

Onodera, Akira; Kawai, Yuichi; Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio

2013-01-01

Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

Energy Technology Data Exchange (ETDEWEB)

Onodera, Akira, E-mail: onodera@pharm.kobegakuin.ac.jp [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kawai, Yuichi [Department of Pharmaceutical Sciences, Kobegakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio [Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871 (Japan)

2013-06-14

Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

Low-dose radiation induces drosophila innate immunity through toll pathway activation

International Nuclear Information System (INIS)

Seong, Ki Moon; Kim, Cha Soon; Lee, Byung-Sub; Nam, Seon Young; Yang, Kwang Hee; Kim, Ji-Young; Jin, Young-Woo; Park, Joong-Jean; Min, Kyung-Jin

2012-01-01

Numerous studies report that exposing certain organisms to low-dose radiation induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing survival after bacterial infection and antimicrobial peptide gene expression in irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances innate immunity. Low-dose irradiation of flies significantly increased resistance against gram-positive and gram-negative bacterial infections, as well as expression of several antimicrobial peptide genes. Additionally, low-dose irradiation also resulted in a specific increase in expression of key proteins of the Toll signaling pathway and phosphorylated forms of p38 and N-terminal kinase (JNK). These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila. (author)

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

International Nuclear Information System (INIS)

Kakehashi, Anna; Wei, Min; Fukushima, Shoji; Wanibuchi, Hideki

2013-01-01

This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P 450 inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

Energy Technology Data Exchange (ETDEWEB)

Kakehashi, Anna; Wei, Min [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan); Fukushima, Shoji [Japan Bioassay Research Center, Japan Industrial Safety and Health Association, 2445 Hirasawa, Hadano, Kanagawa 257-0015 (Japan); Wanibuchi, Hideki, E-mail: wani@med.osaka-cu.ac.jp [Department of Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-Ku, Osaka 545-8585 (Japan)

2013-10-28

This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P{sub 450} inducers, such as phenobarbital, α-benzene hexachloride and 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

Radiation-induced hypopituitarism is dose-dependent

International Nuclear Information System (INIS)

Littley, M.D.; Shalet, S.M.; Beardwell, C.G.; Robinson, E.L.; Sutton, M.L.

1989-01-01

Radiation-induced hypopituitarism has been studies prospectively for up to 12 years in 251 adult patients treated for pituitary disease with external radiotherapy, ranging in dose from 20 Gy in eight fractions over 11 days to 45 Gy in 15 fractions over 21 days. Ten further patients were studied 2-4 years after whole-body irradiation for haematological malignancies using 12 Gy in six fractions over 3 days and seven patients were studied 3-11 years after whole-brain radiotherapy for a primary brain tumour (30 Gy, eight fractions, 11 days). Five years after treatment, patients who received 20 Gy had an incidence of TSH deficiency of 9% and in patients treated with 35-37 Gy, 40 Gy and 42-45 Gy, the incidence of TSH deficiency increased significantly with increasing dose. A similar relationship was observed for both ACTH and gonadotrophin deficiencies when the 20 Gy group was compared to patients treated with 35-45 Gy. Growth hormone deficiency was universal by 5 years over the dose range 35-45 Gy. In seven patients who were treated with 30 Gy in eight fractions over 11 days, deficiencies were observed at a similar frequency to the 40 Gy group (15 fractions, 21 days). No evidence of pituitary dysfunction was detected in the ten patients who received 12 Gy (six fractions, 3 days). (author)

Low-dose radiation-induced endothelial cell retraction

International Nuclear Information System (INIS)

Kantak, S.S.; Onoda, J.M.; Diglio, C.A.; Harper Hospital, Detroit, MI

1993-01-01

The data presented here are representative of a series of studies designed to characterize low-dose radiation effects on pulmonary microvascular endothelium. Data suggest that post-irradiation lung injuries (e.g. oedema) may be induced with only a single fraction of therapeutic radiation, and thus microscopic oedema may initiate prior to the lethal effects of radiation on the microvascular endothelium, and much earlier than would be suggested by the time course for clinically-detectable oedema. (author)

Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

Energy Technology Data Exchange (ETDEWEB)

Li, Jun; Sun, Kang [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Ni, Lijuan; Wang, Xufang [School of Chemistry and Materials of Science, University of Science and Technology of China, Hefei 230052, Anhui (China); Wang, Dongxu [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China); Zhang, Jinsong, E-mail: zjs@ahau.edu.cn [School of Tea and Food Science, Anhui Agricultural University, Hefei 230036, Anhui (China)

2012-02-01

Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.

Sodium selenosulfate at an innocuous dose markedly prevents cisplatin-induced gastrointestinal toxicity

International Nuclear Information System (INIS)

Li, Jun; Sun, Kang; Ni, Lijuan; Wang, Xufang; Wang, Dongxu; Zhang, Jinsong

2012-01-01

Our previous studies in mice revealed that two weeks short-term toxicity of sodium selenosulfate was significantly lower than that of sodium selenite, but selenium repletion efficacy of both compounds was equivalent. In addition, we showed that sodium selenosulfate reduced nephrotoxicity of cisplatin (CDDP) without compromising its anticancer activity, thus leading to a dramatic increase of cancer cure rate from 25% to 75%. Hydration has been used in clinical practice to reduce CDDP-induced nephrotoxicity, but it cannot mitigate CDDP-induced gastrointestinal toxicity. The present work investigated whether sodium selenosulfate is a potential preventive agent for the gastrointestinal toxicity. In tumor-bearing mice, sodium selenosulfate was administered at a dose of 9.5 μmol/kg daily for 11 days, CDDP alone resulted in diarrhea by 88% on day 12, whereas the co-administration of CDDP and sodium selenosulfate dramatically reduced diarrhea to 6% (p < 0.0001). Such a prominent protective effect promoted us to evaluate the safety potential of long-term sodium selenosulfate application. Mice were administered with sodium selenosulfate or sodium selenite for 55 days at the doses of 12.7 and 19 μmol/kg. The low-dose sodium selenite caused growth suppression and hepatotoxicity which were aggravated by the high-dose, leading to 40% mortality rate, but no toxic symptoms were observed in the two sodium selenosulfate groups. Altogether these results clearly show that sodium selenosulfate at an innocuous dose can markedly prevent CDDP-induced gastrointestinal toxicity. -- Highlights: ►Cisplatin resulted in diarrhea in mice by 88%. ►i.p. selenosulfate at 9.5 μmol/kg daily for 11 days reduced diarrhea to 6%. ►i.p. selenosulfate at 19 μmol/kg daily for 55 days was not toxic. ►i.p. selenite at 19 μmol/kg daily for 55 days was lethal. ►Innocuous dose of selenosulfate greatly prevents cisplatin-induced diarrhea.

Effects of Respiration-Induced Density Variations on Dose Distributions in Radiotherapy of Lung Cancer

International Nuclear Information System (INIS)

Mexner, Vanessa; Wolthaus, Jochem W.H.; Herk, Marcel van; Damen, Eugene M.F.; Sonke, Jan-Jakob

2009-01-01

Purpose: To determine the effect of respiration-induced density variations on the estimated dose delivered to moving structures and, consequently, to evaluate the necessity of using full four-dimensional (4D) treatment plan optimization. Methods and Materials: In 10 patients with large tumor motion (median, 1.9 cm; range, 1.1-3.6 cm), the clinical treatment plan, designed using the mid-ventilation ([MidV]; i.e., the 4D-CT frame closest to the time-averaged mean position) CT scan, was recalculated on all 4D-CT frames. The cumulative dose was determined by transforming the doses in all breathing phases to the MidV geometry using deformable registration and then averaging the results. To determine the effect of density variations, this cumulative dose was compared with the accumulated dose after similarly deforming the planned (3D) MidV-dose in each respiratory phase using the same transformation (i.e., 'blurring the dose'). Results: The accumulated tumor doses, including and excluding density variations, were almost identical. Relative differences in the minimum gross tumor volume (GTV) dose were less than 2% for all patients. The relative differences were even smaller in the mean lung dose and the V20 (<0.5% and 1%, respectively). Conclusions: The effect of respiration-induced density variations on the dose accumulated over the respiratory cycle was very small, even in the presence of considerable respiratory motion. A full 4D-dose calculation for treatment planning that takes into account such density variations is therefore not required. Planning using the MidV-CT derived from 4D-CT with an appropriate margin for geometric uncertainties is an accurate and safe method to account for respiration-induced anatomy variations.

Radiation retinopathy caused by low dose irradiation and antithyroid drug-induced systemic vasculitis

International Nuclear Information System (INIS)

Sonoda, Koh-hei; Ishibashi, Tatsuro

2005-01-01

We report on a patient with Graves' disease with radiation retinopathy caused by low-dose irradiation and antithyroid drug-induced antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. A 38-year-old woman with Graves' disease presented with bilateral blurred vision, micro-aneurysms, telangiectasia, and macular edema. The patient was examined by ophthalmoscopy and fluorescein angiography, and radiation retinopathy was diagnosed. The patient had been treated with low-dose irradiation for her Graves' ophthalmopathy a few years earlier. She also had ANCA-positive vasculitis induced by the antithyroid drug (propylthiouracil, PTU) that had been prescribed for her at that time. Because of multiple avascular areas on both retinas, she was treated by intensive retinal photocoagulation to control progressive retinopathy. The radiation doses used to treat Graves' disease ophthalmopathy are low. Nevertheless, there is still a risk of radiation retinopathy developing in patients with PTU-induced ANCA-positive vasculitis. (author)

Low dose radiation induced protein and its experimental and ophthalmic clinical research

International Nuclear Information System (INIS)

Shen Wei; Su Liaoyuan; Liu Fenju; Ding Jie; Li Longbiao; Pan Chengsi

2001-01-01

The protective effects of low dose radiation (LDR) induced protein on cellular impairments caused by some harmful chemical and physical factors were studied. Male Kunming mice were irradiated with LDR, then the spleen cells of the mice were broken with ultrasonic energy and then ultracentrifugalized. The supernatant solution contained with LDR induced protein. The newly emerging protein was detected by gel filtration and its molecular weight was determined by gel electrophoresis. The content of newly emerging protein (LDR induced protein) was determined by Lowry's method. The method of isotope incorporation was used to observe the biological activity and its influence factors, the protective effects of LDR induced protein on the cells impaired by irradiating with ultraviolet (UV), high doses of 60 Co γ-rays and exposed to heat respectively, and the stimulative effects of LDR induced protein on human peripheral blood lymphocytes. Newly emerging protein has been observed in the experiment. The molecular weight of the protein is in the region 76.9 KD+- - 110.0 KD+-, the yield of the protein was 613.33 +- 213.42 μg per 3 x 10 7 spleen cells. DPM values (isotope were incorporated) of normal and injured mice spleen cells increased significantly after stimulating with the solution contained LDR induced protein. It is concluded that LDR induced protein could be obtained from mice spleen cells exposed to 5 - 15 cGy radiation for 2 - 16 h. The protein had biological activity and was able to stimulate the transformation of the spleen cells in vitro. It had obvious protective effects on some impaired cells caused by high dose radiation, UV radiation, heat and so on. It also had stimulative effects on the transformation of peripheral blood T and B lymphocytes of healthy individual and patients with eye diseases. It indicates that LDR induced protein increased immune function of human

Relaxation behavior and dose dependence of radiation induced radicals in irradiated mango

International Nuclear Information System (INIS)

Kameya, Hiromi; Kakita, Daisuke; Kaimori, Yoshihiko; Ukai, Mitsuko; Kikuchi, Masahiro; Kobayashi, Yasuhiko; Shimoyama, Yuhei

2010-01-01

Mangoes are imported to Japan after treated with hot water. Recently, irradiated mangoes imported to U. S. are widely used. This paper reports on the ESR method for analyzing the radiation induced radicals of irradiated mangoes. Upon the γ ray irradiation, a strong single peak in the flesh and skin of mangoes was observed at g=2.004. This singlet peak may be attributed to organic free radicals. The ESR spectra of the flesh and skin of mangoes showed the radiation induced radicals due to cellulose by irradiation over 12 kGy. The relaxation times (T 1 and T 2 ) of the singlet signal were calculated. T 2 showed dose response according to increasing the irradiation dose levels, while T 1 was almost constant. The value of (T 1 T 2 ) 1/2 showed the dependence of irradiation dose level. (author)

Low dose radiation prevents doxorubicin-induced cardiotoxicity.

Science.gov (United States)

Jiang, Xin; Hong, Yaqiong; Zhao, Di; Meng, Xinxin; Zhao, Lijing; Du, Yanwei; Wang, Zan; Zheng, Yan; Cai, Lu; Jiang, Hongyu

2018-01-02

This study aimed to develop a novel and non-invasive approach, low-dose radiation (LDR, 75 mGy X-rays), to prevent doxorubicin (DOX)-induced cardiotoxicity. BALB/c mice were randomly divided into five groups, Control, LDR (a single exposure), Sham (treated same as LDR group except for irradiation), DOX (a single intraperitoneal injection of DOX at 7.5 mg/kg), and LDR/DOX (received LDR and 72 h later received DOX). Electrocardiogram analysis displayed several kinds of abnormal ECG profiles in DOX-treated mice, but less in LDR/DOX group. Cardiotoxicity indices included histopathological changes, oxidative stress markers, and measurements of mitochondrial membrane permeability. Pretreatment of DOX group with LDR reduced oxidative damages (reactive oxygen species formation, protein nitration, and lipid peroxidation) and increased the activities of antioxidants (superoxide dismutase and glutathione peroxidase) in the heart of LDR/DOX mice compared to DOX mice. Pretreatment of DOX-treated mice with LDR also decreased DOX-induced cardiac cell apoptosis (TUNEL staining and cleaved caspase-3) and mitochondrial apoptotic pathway (increased p53, Bax, and caspase-9 expression and decreased Bcl2 expression and ΔΨm dissipation). These results suggest that LDR could induce adaptation of the heart to DOX-induced toxicity. Cardiac protection by LDR may attribute to attenuate DOX-induced cell death via suppressing mitochondrial-dependent oxidative stress and apoptosis signaling.

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Science.gov (United States)

Shuryak, Igor; Sachs, Rainer K.; Hlatky, Lynn; Mark P. Little; Hahnfeldt, Philip; Brenner, David J.

2006-01-01

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose

Total-dose radiation-induced degradation of thin film ferroelectric capacitors

International Nuclear Information System (INIS)

Schwank, J.R.; Nasby, R.D.; Miller, S.L.; Rodgers, M.S.; Dressendorfer, P.V.

1990-01-01

Thin film PbZr y Ti 1-y O 3 (PZT) ferroelectric memories offer the potential for radiation-hardened, high-speed nonvolatile memories with good retention and fatigue properties. In this paper we explore in detail the radiation hardness of PZT ferroelectric capacitors. Ferroelectric capacitors were irradiated using x-ray and Co-60 sources to dose levels up to 16 Mrad(Si). The capacitors were characterized for their memory properties both before and after irradiation. The radiation hardness was process dependent. Three out of four processes resulted in capacitors that showed less than 30% radiation-induced degradation in retained polarization charge and remanent polarization after irradiating to 16 Mrad(Si). On the other hand, one of the processes showed significant radiation-induced degradation in retained polarization charge and remanent polarization at dose levels above 1 Mrad(Si). The decrease in retained polarization charge appears to be due to an alteration of the switching characteristics of the ferroelectric due to changes in the internal fields. The radiation-induced degradation is recoverable by a postirradiation biased anneal and can be prevented entirely if devices are cycled during irradiation. The authors have developed a model to simulate the observed degradation

Evaluation of Interindividual Human Variation in Bioactivation and DNA Adduct Formation of Estragole in Liver Predicted by Physiologically Based Kinetic/Dynamic and Monte Carlo Modeling

NARCIS (Netherlands)

Punt, Ans; Paini, Alicia; Spenkelink, Bert; Scholz, Gabriele; Schilter, Benoit; Bladeren, Van Peter J.; Rietjens, Ivonne M.C.M.

2016-01-01

Estragole is a known hepatocarcinogen in rodents at high doses following metabolic conversion to the DNA-reactive metabolite 1′-sulfooxyestragole. The aim of the present study was to model possible levels of DNA adduct formation in (individual) humans upon exposure to estragole. This was done by

Diethylnitrosamine initiation does not alter clofibric acid-induced hepatocarcinogenesis in the rat.

Science.gov (United States)

Michel, Cecile; Desdouets, Chantal; Slaoui, Mohamed; Isaacs, Kevin Robert; Roberts, Ruth Angela; Boitier, Eric

2007-09-01

Clofibric acid (CLO) is a nongenotoxic hepatocarcinogen in rodents that causes altered hepatocellular foci and/or neoplasms. Initiation by DNA-damaging agents such as diethylnitrosamine (DEN) accelerates focus and tumor appearance and could therefore significantly contribute to shortening of the regulatory 2-year rodent carcinogenicity bioassays. However, it is crucial to evaluate the histological and molecular impact of initiation with DEN on hepatocarcinogenesis promoted by CLO. Male F344 rats were given a single nonnecrogenic injection of DEN (0 or 30 mg/kg) followed by Control diet or CLO (5000 ppm) in diet for up to 20 months. Histopathology and gene expression profiling were performed in liver tumors and surrounding nontumoral liver tissues. The molecular signature of DEN was characterized and its histopathological and immunohistopathological effects on focus and tumor types were also determined. Although foci and tumors appeared earlier in the DEN+CLO-treated group compared to the group treated with CLO alone, DEN had little impact on gene expression in nontumoral tissues since the gene expression profiles were highly similar between Control and DEN-treated rats, and DEN+CLO- and CLO-treated rats. Finally, tumors obtained from DEN+CLO and CLO-treated groups displayed highly correlated gene expression profiles (r>0.83, independently of the time-point). The pathways involved in tumor development revealed by Gene Ontology functional analysis are similar when driven either by spontaneous initiation or by a chemically induced initiation step. Our work described here may contribute to the design optimization of shorter preclinical tests for the evaluation of the nongenotoxic hepatocarcinogenic potential of drugs under development.

Risk of radiation-induced cancer at low doses and low dose rates for radiation protection purposes

International Nuclear Information System (INIS)

1995-01-01

The aim of this report is to provide an updated, comprehensive review of the data available for assessing the risk of radiation-induced cancer for radiation protection purposes. Particular emphasis is placed on assessing risks at low doses and low dose rates. The review brings together the results of epidemiological investigations and fundamental studies on the molecular and cellular mechanisms involved in radiation damage. Additionally, this information is supplemented by studies with experimental animals which provide further guidance on the form of the dose-response relationship for cancer induction, as well as on the effect of dose rate on the tumour yield. The emphasis of the report is on cancer induction resulting from exposure to radiations with a low linear energy transfer (LET). The work was performed under contract for the Institut de Protection et de Surete Nucleaire, Fontenay-aux-Roses, Paris, France, whose agreement to publish is gratefully ackowledged. It extends the advice on radiation risks given in Documents of the NRPB, 4 No. 4 (1993). (Author)

Cystoid Macular Edema Induced by Low Doses of Nicotinic Acid

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Daniela Domanico

2013-01-01

Full Text Available Cystoid macular edema (CME is a condition that involves the macula, causing painless vision loss. In this paper, we report a case of niacin-induced bilateral cystoid macular edema (CME in a middle-age woman taking low dose of niacin (18 mg of nicotinic acid. Optical coherence tomography (OCT showed retinal thickening and cystoid spaces in both eyes, whereas fluorescein angiography (FA; HRA 2, Heidelberg Engineering revealed the absence of fluorescein leakage also in later phases. Four weeks after discontinuation of therapy there were a complete disappearance of macular edema at funduscopic examination and an improvement of visual acuity in both eyes. Furthermore OCT showed a normal retinal profile in both eyes. In our opinion considering the wide availability of niacin, medical monitoring and periodical examination should be considered during niacin administration. To our knowledge, this is the first report in the literature that described the very low-dose niacin-induced bilateral niacin maculopathy.

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience.

Science.gov (United States)

Filipczak-Bryniarska, Iwona; Krzyzewski, Roger M; Kucharz, Jakub; Michalowska-Kaczmarczyk, Anna; Kleja, Justyna; Woron, Jarosław; Strzepek, Katarzyna; Kazior, Lucyna; Wordliczek, Jerzy; Grodzicki, Tomasz; Krzemieniecki, Krzysztof

2017-08-17

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m 2 . Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Mechanism involved in trichloroethylene-induced liver cancer: Importance to environmental cleanup. 1998 annual progress report

International Nuclear Information System (INIS)

Bull, R.J.; Miller, J.H.; Sasser, L.B.; Schultz, I.R.; Thrall, B.D.

1998-01-01

'The objective of this project is to develop critical data for changing risk-based clean-up standards for trichloroethylene (TCE). The project is organized around two interrelated tasks: Task 1 addresses the tumorigenic and dosimetry issues for the metabolites of TCE that produce liver cancer in mice, dichloroacetate (DCA) and trichloroacetate (TCA). Early work had suggested that TCA was primarily responsible for TCE-induced liver tumors, but several, more mechanistic observations suggest that DCA may play a prominent role. This task is aimed at determining the basis for the selection hypothesis and seeks to prove that this mode of action is responsible for TCE-induced tumors. This project will supply the basic dose-response data from which low-dose extrapolations would be made. Task 2 seeks specific evidence that TCA and DCA are capable of promoting the growth of spontaneously initiated cells from mouse liver, in vitro. The data provide the clearest evidence that both metabolites act by a mechanism of selection rather than mutation. These data are necessary to select between a linear (i.e. no threshold) and non-linear low-dose extrapolation model. As of May of 1998, this research has identified two plausible modes of action by which TCE produces liver tumors in mice. These modes of action do not require the compounds to be mutagenic. The bulk of the experimental evidence suggests that neither TCE nor the two hepatocarcinogenic metabolites of TCE are mutagenic. The results from the colony formation assay clearly establish that both of these metabolites cause colony growth from initiated cells that occur spontaneously in the liver of B 6 C 3 F 1 mice, although the phenotypes of the colonies differ in the same manner as tumors differ, in vivo. In the case of DCA, a second mechanism may occur at a lower dose involving the release of insulin. This observation is timely as it was recently reported that occupational exposures to trichloroethylene results in 2 to 4-fold

Mechanisms and biological importance of photon-induced bystander responses. Do they have an impact on low-dose radiation responses

International Nuclear Information System (INIS)

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced by-stander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. (author)

Dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro

International Nuclear Information System (INIS)

Liu Shuchun; Lu Zhe; Li Yanbo; Kang Shunai; Gong Shouliang; Zhao Wenju

2008-01-01

Objective: To observe the dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro in order to reveal the possible mechanism of biological effect and adaptive response induced by low dose radiation. Methods: The experiment was divided into D2 (challenging dose), D1 (inductive dose) + D2 and sham-irradiation groups. EL-4 lymphoma cells were irradiated with D1 (75 mGy, 6.25-200.00 mGy·mm -1 ) and D2(1.5 Gy, 287 mGy·min -1 ), the time interval between D1 and D2 was 6 h. The percentage of apoptosis and each cell cycle phase were measured with flow cytometry. Results: When the dose rates of D1 were 6.25-50.00 mGy·min -1 , the percentages of apoptosis in the D1 + D2 group were significantly lower than those in the D2 group (P 0 /G 1 phase cells decreased significantly (P -1 , D2 is 1.5 Gy (287 mGy·min -1 ), and the time interval between D1 and D2 is 6 h, the adaptive response of apoptosis and cell cycle progression in EL-4 lymphoma cells in vitro could be induced. (authors)

Correlation between induced embryo toxicity and absorption dose of enriched uranium in testes

International Nuclear Information System (INIS)

Zhu Shoupeng; Lun Mingyue

1996-01-01

Doses of enriched uranium in testes inducing dominant lethality and skeletal abnormalities in offsprings are estimated. When intra-testicular injection dose is 0.4∼60 μg enriched uranium; from intake to insemination, testes could receive 9.14 x 10 -5 ∼1.38 x 10 -2 Gy radiation dose. Experimental results show that with the increase in the absorption dose, the number of living fetuses in a litter decreases, dominant lethality and skeletal abnormalities rise. It should be noted that relationship between the injected dose (I in μg) and the incidence of dominant skeletal abnormalities (S in %) in the offsprings can be represented by equation: S = 28.84 + 0.84I

Correlation between induced embryo toxicity and absorption dose of enriched uranium in testes

Energy Technology Data Exchange (ETDEWEB)

Shoupeng, Zhu; Mingyue, Lun [Suzhou Medical Coll., JS (China)

1996-08-01

Doses of enriched uranium in testes inducing dominant lethality and skeletal abnormalities in offsprings are estimated. When intra-testicular injection dose is 0.4{approx}60 {mu}g enriched uranium; from intake to insemination, testes could receive 9.14 x 10{sup -5}{approx}1.38 x 10{sup -2} Gy radiation dose. Experimental results show that with the increase in the absorption dose, the number of living fetuses in a litter decreases, dominant lethality and skeletal abnormalities rise. It should be noted that relationship between the injected dose (I in {mu}g) and the incidence of dominant skeletal abnormalities (S in %) in the offsprings can be represented by equation: S = 28.84 + 0.84I.

Frequencies of aneuploidy and dominant lethal mutations in young female mice induced by low dose γ-rays

International Nuclear Information System (INIS)

Yao Suyan; Zhang Chaoyang; Dai Lianlian; Gao Changwen

1991-01-01

Relationship between aneuploidy, dominant lethal mutations and doses in young feral mice induced by low dose γ-rays was examined. The results suggest that the frequencies of aneuploidy of embryos increased at 0.15 Gy, but increases at over 0.50 Gy after irradiation in groups. The frequencies of aneuploidy and dominant lethal mutations increased with increasing doses and fitted linear relationship. This dose-response relationship of trisomic was not significant. The frequency of dominant lethal mutations induced by 60 Co γ irradiation is 5.59%. The effect of dominant lethal mutation is higher than that of the aneuploidy

Diethylene glycol-induced toxicities show marked threshold dose response in rats

Energy Technology Data Exchange (ETDEWEB)

Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)

2015-02-01

Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.

Radiation effect and response of DNA synthesis in lymphocytes induced by low dose irradiation

International Nuclear Information System (INIS)

Zhao Yujie; Su Liaoyuan; Zou Huawei; Kong Xiangrong

1999-01-01

The ability of DNA synthesis in lymphocytes were measured by using 3 H-TdR incorporation method. This method was used to observe the damage of lymphocytes irradiated by several challenge doses (0.5-0.8 Gy) and adaptive response induced by previous low dose irradiation. The results show that DNA synthesis was inhibited by challenge dose of radiation and was adapted by previous 0.048 Gy irradiation

Studies on chromosome aberrations induced in human lymphocytes by very low-dose exposure to tritium

International Nuclear Information System (INIS)

Hori, T.; Moriya, Junko; Nakai, Sayaka

1978-01-01

Assessment of potential hazard from environmental tritium to man becomes very important with increasing the development of nuclear-power industry. However, little data are available as to the determination on the genetic effect of tritium especially at the low levels. The object of the present study is to obtain quantitative data for chromosome aberrations in human lymphocytes, as an indicator for genetic risk estimation, induced by tritium at very low dose levels. Leukocyte cultures of human peripheral blood were chronically exposed for 48h to tritiated water and 3 H-thymidine using a wide range of tritium doses, and aberrations in lymphocyte chromosomes at the first metaphases were examined. In the experimental conditions, the types of aberrations induced by radiation emitted from both tritiated water and 3 H-thymidine were mostly chromatid types, such as chromatid gaps and deletions. The dose-response relations for chromatid breaks per cell exhibited unusual dose-dependency in both cases. It was demonstrated that at higher dose range the yields of chromatid breaks increased linearly with dose, while those at lower dose range were significantly higher than would be expected by a downward extraporation from the linear relation. Partial-hit or partial-target kinetics events appeared at very low dose exposure. (author)

Immunologic mechanism of the suppressive effect of low dose radiation on thymic lymphoma induced by radiation

International Nuclear Information System (INIS)

Li Xiujuan; Yang Ying; Li Xiuyi; Liu Shuzheng

1999-01-01

To study immunologic mechanism of the suppressive effect of low dose radiation (LDR) on thymic lymphoma (TL) induced by high dose radiation (HDR). The authors adopted the model that C57BL/6J mice were administered whole body irradiation with 1.75 Gy X-rays one time every week for 4 weeks to induce TL. It was examined that splenic NK cytotoxic activity, IL-2 and γ-IFN secretion activity, peritoneal macrophage phagocytosis and its TNF-α secretion activity in mice with different dose 1 month after irradiation. The results showed that all the immunologic functions mentioned above in mice given 75 mGy 12 h before 1.75 Gy every time were higher than that in mice given only 1.75 Gy, and approached to the sham-irradiation mice. It suggested that the suppressive effect of LDR on TL induced by HDR may be related to the adaptive response induced by LDR and decreasing immunological functions damage caused by HDR

Oxidative Stress in the Carcinogenicity of Chemical Carcinogens

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Hideki Wanibuchi

2013-10-01

Full Text Available This review highlights several in vivo studies utilizing non-genotoxic and genotoxic chemical carcinogens, and the mechanisms of their high and low dose carcinogenicities with respect to formation of oxidative stress. Here, we survey the examples and discuss possible mechanisms of hormetic effects with cytochrome P450 inducers, such as phenobarbital, a-benzene hexachloride and 1,1-bis(p-chlorophenyl-2,2,2-trichloroethane. Epigenetic processes differentially can be affected by agents that impinge on oxidative DNA damage, repair, apoptosis, cell proliferation, intracellular communication and cell signaling. Non-genotoxic carcinogens may target nuclear receptors and induce post-translational modifications at the protein level, thereby impacting on the stability or activity of key regulatory proteins, including oncoproteins and tumor suppressor proteins. We further discuss role of oxidative stress focusing on the low dose carcinogenicities of several genotoxic carcinogens such as a hepatocarcinogen contained in seared fish and meat, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, arsenic and its metabolites, and the kidney carcinogen potassium bromate.

Study of the effect of dose-rate on radiation-induced damage to human erythrocytes

Energy Technology Data Exchange (ETDEWEB)

Krokosz, Anita [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland)]. E-mail: krokosz@biol.uni.lodz.pl; Koziczak, Renata [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland); Gonciarz, Marta [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland); Szweda-Lewandowska, Zofia [Department of Molecular Biophysics, University of Lodz, Banacha 12/16, Lodz (Poland)

2006-01-15

Human erythrocytes suspended in an isotonic Na-phosphate buffer, pH 7.4 (hematocrit of 2%) were irradiated with {gamma}-rays at three dose-rates of 66.7, 36.7, 25 Gy min{sup -1} in order to investigate the influence of the dose-rate on radiation-induced membrane damage, hemoglobin oxidation and loss of reduced glutathione. The obtained results showed that such processes as erythrocyte hemolysis, lipid and protein destruction depend on the radiation dose-rate. The parameter values describing these processes showed an inverse dose-rate effect.

Study of the effect of dose-rate on radiation-induced damage to human erythrocytes

International Nuclear Information System (INIS)

Krokosz, Anita; Koziczak, Renata; Gonciarz, Marta; Szweda-Lewandowska, Zofia

2006-01-01

Human erythrocytes suspended in an isotonic Na-phosphate buffer, pH 7.4 (hematocrit of 2%) were irradiated with γ-rays at three dose-rates of 66.7, 36.7, 25 Gy min -1 in order to investigate the influence of the dose-rate on radiation-induced membrane damage, hemoglobin oxidation and loss of reduced glutathione. The obtained results showed that such processes as erythrocyte hemolysis, lipid and protein destruction depend on the radiation dose-rate. The parameter values describing these processes showed an inverse dose-rate effect

Mechanisms of Low Dose Radiation-induced T helper Cell Function

International Nuclear Information System (INIS)

Gridley, Daila S.

2008-01-01

Exposure to radiation above levels normally encountered on Earth can occur during wartime, accidents such as those at Three Mile Island and Chernobyl, and detonation of 'dirty bombs' by terrorists. Relatively high levels of radiation exposure can also occur in certain occupations (low-level waste sites, nuclear power plants, nuclear medicine facilities, airline industry, and space agencies). Depression or dysfunction of the highly radiosensitive cells of the immune system can lead to serious consequences, including increased risk for infections, cancer, hypersensitivity reactions, poor wound healing, and other pathologies. The focus of this research was on the T helper (Th) subset of lymphocytes that secrete cytokines (proteins), and thus control many actions and interactions of other cell types that make up what is collectively known as the immune system. The Department of Energy (DOE) Low Dose Radiation Program is concerned with mechanisms altered by exposure to high energy photons (x- and gamma-rays), protons and electrons. This study compared, for the first time, the low-dose effects of two of these radiation forms, photons and protons, on the response of Th cells, as well as other cell types with which they communicate. The research provided insights regarding gene expression patterns and capacity to secrete potent immunostimulatory and immunosuppressive cytokines, some of which are implicated in pathophysiological processes. Furthermore, the photon versus proton comparison was important not only to healthy individuals who may be exposed, but also to patients undergoing radiotherapy, since many medical centers in the United States, as well as worldwide, are now building proton accelerators. The overall hypothesis of this study was that whole-body exposure to low-dose photons (gamma-rays) will alter CD4+ Th cell function. We further proposed that exposure to low-dose proton radiation will induce a different pattern of gene and functional changes compared to

Dose-dependent effects of celecoxib on CB-1 agonist-induced antinociception in the mice

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Mohammad Reza Zarrindast

2009-04-01

Full Text Available "nObjective: Endocannabinoid produce analgesia that is comparable which of opioids. The mechanism of antinociceptive effects of (∆ - 9 tetrahydrocannabinol (THC is suggested to be through cyclooxygenase (COX pathway. In the present work, the effect of two extreme dose ranges of celecoxib (mg/kg and ng/kg, a cyclooxygenase-2 (COX-2 antagonist, on arachidonylcyclopropylamide (ACPA, a selective CB1 agonist induced antinociception in mice was examined. "nMethods: We have investigated the interaction between celecoxib, at the doses of mg/kg (50, 100, 200 and 400 i.p.  and ultra low dose (ULD (25 and 50 ng/kg, i.p., on the antinociceptive effect of intracerebroventricular (i.c.v. administration of ACPA (0.004, 0.0625 and 1 μg/mice, using formalin test in mice. "nResults: I.C.V. administration of ACPA induced antinociception. Intraperitoneal administration of celecoxib (mg/kg and its ULD (ng/kg attenuated and potentiated, ACPA antinociceptive effects, respectively. "nConclusion: It is concluded that the mg/kg doses of COX-2 antagonist showed opposite effects compare to the ultra-low dose of the drug.

Search for the lowest irradiation dose from literatures on radiation-induced cancer in uterus

International Nuclear Information System (INIS)

Yoshizawa, Yasuo; Kusama, Tomoko

1975-01-01

A survey of past case reports on radiation-induced cancer of the uterus was carried out with the main object of finding the lowest irradiation dose. Search of literature published since 1912 revealed 548 cases of radiation-induced cancer of the uterus. All of these cases of radiation-induced cancer had received radiation for the treatment of non-malignant disease. The primary gynecological conditions which were the object of radiation therapy were functional bleeding, endometrial hyperplasia, myoma, endometritis, and polyps. The lowest irradiation dose was estimated at 1000-1450 rad in the case of external X-ray irradiation, and 100 mg.hr for intrauterine radium therapy, which corresponds to 100-1000 rad. It was noted that were more cases of corpus cancer than cervical cancer. Histopathological findings of radiation-induced uterine cancer were carcinoma, sarcoma, and mixed mesodermal tumors. The latent period was distributed in the range of 1 to 40 years, with the average of 10.1 years. (auth.)

Dose-response relationship of γ-ray-induced reciprocal translocations at low doses in spermatogonia of the crab-eating monkey (Macaca fascicularis)

International Nuclear Information System (INIS)

Matsuda, Yoichi; Tobari, Izuo; Yamagiwa, Junji; Utsugi, Toyoko; Okamoto, Masanori; Nakai, Sayaka

1985-01-01

The yield of translocations induced by acute γ-irradiation at low doses in the crab-eating monkey's (Macaca fascicularis) spermatogonia was examined. Over the low dose range from 0 to 1 Gy, the dose-response relationship for translocation yield was a linear one. To estimate the sensitivity to the induction of translocations in the crab-eating monkey's spermatogonia, the slope of the regression line was compared with those in other mammalian species. Consequently, over the low dose range below 1 Gy, the sensitivity of the crab-eating monkey's spermatogonia to translocation induction was similar to several mammalian species, the mouse, Chinese hamster, and the rabbit, but significantly higher than that of the rhesus monkey and lower than that of the marmoset. (Auth.)

Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

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Iva Bozic

2015-01-01

Full Text Available Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation.

Low-Dose Ribavirin Treatments Attenuate Neuroinflammatory Activation of BV-2 Cells by Interfering with Inducible Nitric Oxide Synthase

Science.gov (United States)

Bozic, Iva; Savic, Danijela; Jovanovic, Marija; Bjelobaba, Ivana; Laketa, Danijela; Nedeljkovic, Nadezda; Stojiljkovic, Mirjana; Pekovic, Sanja; Lavrnja, Irena

2015-01-01

Microglia play a key role in defending central nervous system from various internal and external threats. However, their excessive and/or chronic activation is associated with deleterious effects in a variety of neurodegenerative diseases. Previously, we have shown that ribavirin when applied in clinically relevant dosage (10 μM) modulates activated microglia in complex fashion inducing both anti- and proinflammatory effects, simultaneously causing cytotoxicity. Here, we examined potential of low-dose ribavirin (0.1 and 1 μM) to modulate activated BV-2 microglia. Morphological and functional activation of BV-2 cells was achieved with lipopolysaccharide (LPS) stimulation. Our results demonstrated that low-dose ribavirin did not induce cell death, while 10 μM ribavirin promoted LPS induced apoptosis. We determined that 1 μM ribavirin was equally efficient in deactivation of LPS induced morphological changes as 10 μM ribavirin treatment. Ribavirin showed halfway success in reducing markers of functional activation of microglia. Namely, none of the doses had effect on LPS triggered production of proinflammatory cytokine tumor necrosis factor alpha. On the other hand, low-dose ribavirin proved its effectiveness in reduction of another inflammatory mediator, nitric oxide, by inhibiting inducible form of nitric oxide synthase. Our results imply that low-dose ribavirin may alleviate nitrosative stress during neuroinflammation. PMID:26413464

Adaptive repair induced by small doses of γ radiation in repair-defective human cells

International Nuclear Information System (INIS)

Zasukhina, G.D.; L'vova, G.N.; Vasil'eva, I.M.; Sinel'shchikova, T.A.; Semyachkina, A.N.

1993-01-01

Adaptive repair induced by small doses of gamma radiation was studied in repair-defective xeroderma pigmentosum, gout, and homocystinuria cells. The adaptation of cells induced by small doses of radiation was estimated after subsequent exposure to gamma radiation, 4-nitroquinoline-1-oxide, and N-methyl-N-nitro-N-nitrosoguanidine by three methods: (1) by the reduction in DNA breaks; (2) by induction of resistant DNA synthesis; and (3) by increased reactivation of vaccinia virus. The three cell types in response to the three different mutagens revealed differences in the mechanism of cell defense in excision repair, in the adaptive response, and in Weigl reactivation

Review of low dose-rate epidemiological studies and biological mechanisms of dose-rate effects on radiation induced carcinogenesis

International Nuclear Information System (INIS)

Iwasaki, Toshiyasu; Otsuka, Kensuke; Yoshida, Kazuo

2015-01-01

Radiation protection system adopts the linear non-threshold model with using dose and dose-rate effectiveness factor (DDREF). The dose-rate range where DDREF is applied is below 100 mGy per hour, and it is regarded that there are no dose-rate effects at very low dose rate, less than of the order of 10 mGy per year, even from the biological risk evaluation model based on cellular and molecular level mechanisms for maintenance of genetic integrity. Among low dose-rate epidemiological studies, studies of residents in high natural background areas showed no increase of cancer risks at less than about 10 mGy per year. On the other hand, some studies include a study of the Techa River cohort suggested the increase of cancer risks to the similar degree of Atomic bomb survivor data. The difference of those results was supposed due to the difference of dose rate. In 2014, International Commission on Radiological Protection opened a draft report on stem cell biology for public consultations. The report proposed a hypothesis based on the new idea of stem cell competition as a tissue level quality control mechanism, and suggested that it could explain the dose-rate effects around a few milligray per year. To verify this hypothesis, it would be needed to clarify the existence and the lowest dose of radiation-induced stem cell competition, and to elucidate the rate of stem cell turnover and radiation effects on it. As for the turnover, replenishment of damaged stem cells would be the important biological process. It would be meaningful to collect the information to show the difference of dose rates where the competition and the replenishment would be the predominant processes. (author)

Clustered DNA damages induced in human hematopoietic cells by low doses of ionizing radiation

Science.gov (United States)

Sutherland, Betsy M.; Bennett, Paula V.; Cintron-Torres, Nela; Hada, Megumi; Trunk, John; Monteleone, Denise; Sutherland, John C.; Laval, Jacques; Stanislaus, Marisha; Gewirtz, Alan

2002-01-01

Ionizing radiation induces clusters of DNA damages--oxidized bases, abasic sites and strand breaks--on opposing strands within a few helical turns. Such damages have been postulated to be difficult to repair, as are double strand breaks (one type of cluster). We have shown that low doses of low and high linear energy transfer (LET) radiation induce such damage clusters in human cells. In human cells, DSB are about 30% of the total of complex damages, and the levels of DSBs and oxidized pyrimidine clusters are similar. The dose responses for cluster induction in cells can be described by a linear relationship, implying that even low doses of ionizing radiation can produce clustered damages. Studies are in progress to determine whether clusters can be produced by mechanisms other than ionizing radiation, as well as the levels of various cluster types formed by low and high LET radiation.

Curcumin Attenuates N-Nitrosodiethylamine-Induced Liver Injury in Mice by Utilizing the Method of Metabonomics.

Science.gov (United States)

Qiu, Peiyu; Sun, Jiachen; Man, Shuli; Yang, He; Ma, Long; Yu, Peng; Gao, Wenyuan

2017-03-08

N-Nitrosodiethylamine (DEN) exists as a food additive in cheddar cheese, processed meats, beer, water, and so forth. It is a potent hepatocarcinogen in animals and humans. Curcumin as a natural dietary compound decreased DEN-induced hepatocarcinogenesis in this research. According to the histopathological examination of liver tissues and biomarker detection in serum and livers, it was demonstrated that curcumin attenuated DEN-induced hepatocarcinogenesis through parts of regulating the oxidant stress enzymes (T-SOD and CAT), liver function (ALT and AST) and LDHA, AFP level, and COX-2/PGE2 pathway. Furthermore, curcumin attenuated metabolic disorders via increasing concentration of glucose and fructose, and decreasing levels of glycine and proline, and mRNA expression of GLUT1, PKM and FASN. Docking study indicated that curcumin presented strong affinity with key metabolism enzymes such as GLUT1, PKM, FASN and LDHA. There were a number of amino acid residues involved in curcumin-targeting enzymes of hydrogen bonds and hydrophobic interactions. All in all, curcumin exhibited a potent liver protective agent inhibiting chemically induced liver injury through suppressing liver cellular metabolism in the prospective application.

Irradiation induced aerosol formation in flue gas: experiments on low doses

International Nuclear Information System (INIS)

Maekelae, J.M.

1992-01-01

Laboratory experiments on irradiation induced aerosol formation from gaseous sulphur dioxide in humid air are presented. This work is connected to the aerosol particle formation process in the electron beam technique for cleaning flue gas. As a partial process of this method primary products of the radiolysis of water vapour convert sulphur dioxide into gaseous sulphuric acid which then nucleates with water vapour forming small acid droplets. This experimental work has been performed on relatively low absorbed doses. Aerosol particle formation is strongly dependent on dose. In the experiments, the first aerosol particles were detected already on absorbed doses of 0.1-10 mGy. The particle size in these cases is in the so-called ultrafine size range (1-20 nm). In this article three experimental set-ups with some characteristic results are presented. (Author)

Dose dependence of radiation-induced segregation in Ni-1 at% Si

International Nuclear Information System (INIS)

Rehn, L.E.; Okamoto, P.R.; Wiedersich, H.

1979-01-01

Measurements have been made of alloy composition as a function of depth from the external surface in Ni-1 at% Si specimens after irradiation with 3-MeV 58 Ni + ions to several different doses at nominal temperatures of 525 and 600 0 C. Very rapid segregation of Si toward the external surface ocurred during irradiation. Surface concentrations of Si in excess of the 10 at% solubility limit were found at both irradiation temperatures after a dose of only approximately 0.05 dpa. The rate of segregation decreased markedly in the dose range from approximately 1-10 dpa. Qualitative agreement was found between the experimental observations and calculations made using a modified Johnson-Lam segregation mode (1976). The present investigation suggests that radiation-induced segregation may significantly alter the mechanical behavior of irradiated alloys long before the onset of void swelling. (Auth.)

Low-dose ionizing radiation alleviates Aβ42-induced defective phenotypes in Drosophila Alzheimer's disease models

International Nuclear Information System (INIS)

Hwang, SooJin; Jeong, Hae Min; Nam, Seon Young

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease that is characterized by amyloid plaques, progressive neuronal loss, and gradual deterioration of memory. Amyloid imaging using positron emission tomography (PET) radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disease, including AD. Particularly, previous studies involving low-dose ionizing radiation on Aβ 42-treated mouse hippocampal neurons have suggested a potential role for low-dose ionizing radiation in the treatment of AD. However, associated in vivo studies involving the therapy effects of low-dose ionizing radiation on AD are still insufficient. As a powerful cell biological system, Drosophila AD models have been generated and established a useful model organism for study on the etiology of human AD. In this study, we investigated the hormesis effects of low-dose ionizing radiation on Drosophila AD models. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation.

Tests of the linearity assumption in the dose-effect relationship for radiation-induced cancer

International Nuclear Information System (INIS)

Cohen, A.F.; Cohen, B.L.

1978-01-01

The validity of the BEIR linear extrapolation to low doses of the dose-effect relationship for radiation induced cancer is tested by use of natural radiation making use of selectivity on type of cancer, sex, age group, geographic area, and time period. For lung cancer, a linear interpolation between zero dose-zero effect and the data from radon-induced cancers in miners over-estimates the total number of observed lung cancers in many countries in the early years of this century; the discrepancy is substantially increased if the 30-44 year age range and/or if only females are considered, and by the fact that many other causes of lung cancer are shown to have been important at that time. The degree to which changes of diagnostic efficiency with time can influence the analysis is considered at some length. It is concluded that the linear relationship substantially over-estimates effects of low radiation doses. A similar analysis is applied to leukemia induced by natural radiation, applying selectivity by age, sex, natural background level, and date, and considering other causes. It is concluded that effects substantially larger than those obtained from linear extrapolation are excluded. The use of the selectivities mentioned above is justified by the fact that the incidence of cancer or leukemia is an upper limit on the rate at which it is caused by radiation effects; in determining upper limits it is justifiable to select situations which minimize it. (author)

The genetic effects induced by an irradiation in low doses at Drosophila melanogaster

International Nuclear Information System (INIS)

Zajnullin, V.G.; Taskaev, A.I.; Moskalev, A.A.; Shaposhnikov, M.V.

2006-01-01

The review generalizes the results obtained in researches of genetic radiation effects for Drosophila melanogaster from contamination regions near the Chernobylsk NPP. The results of laboratory investigations of low dose irradiation effects on genotype variability and lifetime of Drosophila are presented too. It supposed that the main effect of low dose irradiation is caused by the induced genetic instability against the background of which the realization of different-directed radiobiological reactions is possible [ru

Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin

DEFF Research Database (Denmark)

Nicoletti, F; Di Marco, R; Conget, I

2000-01-01

We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every...... induced in vivo by ConA, reducing the levels of IFN-gamma, IL-2 and TNF-alpha and augmenting the level of IL-6. However, only the inhibitory effect of the drug on the synthesis/release of IFN-gamma seemed to be causally related to its capacity to counteract the SZ-induced DM. In fact, the disease...... other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice...

Evaluation of repeated dose micronucleus assays of the liver using N-nitrosopyrrolidine: a report of the collaborative study by CSGMT/JEMS.MMS.

Science.gov (United States)

Ogawa, Izumi; Hagioa, Soichiro; Furukawa, Satoshi; Abe, Masayoshi; Kuroda, Yusuke; Hayashi, Seigo; Wako, Yumi; Kawasako, Kazufumi

2015-03-01

The repeated dose liver micronucleus (RDLMN) assay has the potential to detect liver carcinogens, and can be integrated into a general toxicological study. To assess the performance of the assay, N-nitrosopyrrolidine (NPYR), a genotoxic hepatocarcinogen, was tested in 14- or 28-day RDLMN assays. NPYR was orally administered to rats at a daily dose of 25, 50 or 100 mg/kg. One day after the last administration, a portion of the liver was removed and hepatocyte micronucleus (MN) specimens were prepared by the new method recently established by Narumi et al. In addition, a bone marrow MN assay and a histopathological examination of the liver were conducted. The detection of Phospho-Histone H3 was performed by immunohistochemistry to evaluate the proliferation rate of hepatocytes. The results showed significant increase in the number of micronucleated hepatocytes and Phospho-Histone H3-positive cells from the lowest dose in both 14- and 28-day RDLMN assays. On the other hand, the bone marrow MN assay yielded a negative result, which was in accordance with the existing report of the bone marrow MN assay using mice. Upon histopathological examination, inflammatory lesions and hypertrophy were noted, which may explain the increase in the hepatocyte proliferation and the enhancement of MN induction by NPYR. Our findings indicate that the RDLMN assay could be a useful tool for comprehensive risk assessment of carcinogenicity by providing information on both genotoxicity and histopathology when integrated into a general repeat dosing toxicity assay.

Possible Protective Effect of Low-dose Gamma Irradiation and Certain Natural Products on Chemically Induced Hepatotoxicity in Rats

International Nuclear Information System (INIS)

Rashed, R.R.A.

2015-01-01

Liver, the largest organ in the human body, is a vital organ that performs more than 500 vital metabolic functions. More than a 1000 drugs of the modern pharmacopoeia can induce liver injury with different clinical presentations. In the most severe cases, drug-induced liver injury may require liver transplantation or lead to death of the patient. Acetaminophen (acetyl-para-amino-phenol, paracetamol, APAP) is safe at therapeutic doses, but accidental or intentional overdose can induce severe hepatotoxicity in both humans and experimental animals. APAP-induced hepatotoxicity is dose related and reproducible in animals, and is thus widely used as a model for experimentally induced hepatotoxicity. Many herbs have been used as natural remedies for the prevention and/or treatment of liver diseases. Herbal drugs gained importance and popularity in recent years because of their safety, efficacy and cost effectiveness. Interestingly, exposure to a small dose or dose rate of radiation was reported to induce stress, perturbing homeostasis. Organisms respond adaptively to such disturbances. The mechanisms by which low-dose radiation (LDR) protects the cells or tissue against subsequent radiation- or drug-induced toxicities have been attributed to its stimulation of various protective molecules such as antioxidants and anti apoptotic. In the light of the above mentioned information, this study was constructed in order to investigate the mechanism(s) of the hepato protective effects offered by each of garlic oil (GO), black seed oil (BO) and sesame oil (SO) each alone or combined with low dose total body gamma (γ)-irradiation against APAP-induced hepatotoxicity in male albino Wistar rats. Preliminary pilot studies were performed prior to the main experimental work; in order to select the effective irradiation dose, the hepato protective natural products and the duration of their administration to be used in the main study. To carry out the main study, 96 rats were randomly

Low submetamorphic doses of dexamethasone and thyroxine induce complete metamorphosis in the axolotl (Ambystoma mexicanum) when injected together.

Science.gov (United States)

Kühn, Eduard R; De Groef, Bert; Grommen, Sylvia V H; Van der Geyten, Serge; Darras, Veerle M

2004-06-01

Entanglement of functions between the adrenal (or interrenal) and thyroid axis has been well described for all vertebrates and can be tracked down up to the level of gene expression. Both thyroid hormones and corticosteroids may induce morphological changes leading to metamorphosis climax in the neotenic Mexican axolotl (Ambystoma mexicanum). In a first series of experiments, metamorphosis was induced with an injection of 25 microg T(4) on three alternate days as judged by a decrease in body weight and tail height together with complete gill resorption. This injection also resulted in elevated plasma concentrations of T(3) and corticosterone. Previous results have indicated that the same dose of dexamethasone (DEX) is ineffective in this regard (Gen. Comp. Endocrinol. 127 (2002) 157). In a second series of experiments low doses of T(4) (0.5 microg) or DEX (5 microg) were ineffective to induce morphological changes. However, when these submetamorphic doses were injected together, morphological changes were observed within one week leading to complete metamorphosis. It is concluded that thyroid hormones combined with corticosteroids are essential for metamorphosis in the axolotl and that only high doses of either thyroid hormone or corticosteroid can induce morphological changes when injected separately.

Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides.

Science.gov (United States)

He, Xiaobo; Xia, Qingsu; Woodling, Kellie; Lin, Ge; Fu, Peter P

2017-10-01

There are 660 pyrrolizidine alkaloids (PAs) and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine) and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation. Copyright © 2017. Published by Elsevier B.V.

Pyrrolizidine alkaloid-derived DNA adducts are common toxicological biomarkers of pyrrolizidine alkaloid N-oxides

Directory of Open Access Journals (Sweden)

Xiaobo He

2017-10-01

Full Text Available There are 660 pyrrolizidine alkaloids (PAs and PA N-oxides present in the plants, with approximately half being possible carcinogens. We previously reported that a set of four PA-derived DNA adducts is formed in the liver of rats administered a series of hepatocarcinogenic PAs and a PA N-oxide. Based on our findings, we hypothesized that this set of DNA adducts is a common biological biomarker of PA-induced liver tumor formation. In this study, we determined that rat liver microsomal metabolism of five hepatocarcinogenic PAs (lasiocarpine, retrorsine, riddelliine, monocrotaline, and heliotrine and their corresponding PA N-oxides produced the same set of DNA adducts. Among these compounds, lasiocarpine N-oxide, retrorsine N-oxide, monocrotaline N-oxide, and heliotrine N-oxide are for first time shown to be able to produce these DNA adducts. These results further support the role of these DNA adducts as potential common biomarkers of PA-induced liver tumor initiation.

Antidiabetic Effect of Fresh Nopal (Opuntia ficus-indica in Low-Dose Streptozotocin-Induced Diabetic Rats Fed a High-Fat Diet

Directory of Open Access Journals (Sweden)

Seung Hwan Hwang

2017-01-01

Full Text Available The objective of the present study was to evaluate α-glucosidase inhibitory and antidiabetic effects of Nopal water extract (NPWE and Nopal dry power (NADP in low-dose streptozotocin- (STZ- induced diabetic rats fed a high-fat diet (HFD. The type 2 diabetic rat model was induced by HFD and low-dose STZ. The rats were divided into four groups as follows: (1 nondiabetic rats fed a regular diet (RD-Control; (2 low-dose STZ-induced diabetic rats fed HFD (HF-STZ-Control; (3 low-dose STZ-induced diabetic rats fed HFD and supplemented with NPWE (100 mg/kg body weight, HF-STZ-NPWE; and (4 low-dose STZ-induced diabetic rats fed HFD and supplemented with comparison medication (rosiglitazone, 10 mg/kg, body weight, HF-STZ-Rosiglitazone. In results, NPWE and NADP had IC50 values of 67.33 and 86.68 μg/mL, both of which exhibit inhibitory activities but lower than that of acarbose (38.05 μg/mL while NPWE group significantly decreased blood glucose levels compared to control and NPDP group on glucose tolerance in the high-fat diet fed rats model (P<0.05. Also, the blood glucose levels of HR-STZ-NPWE group were significantly lower (P<0.05 than HR-STZ-Control group on low-dose STZ-induced diabetic rats fed HFD. Based on these findings, we suggested that NPWE could be considered for the prevention and/or treatment of blood glucose and a potential use as a dietary supplement.

Antidiabetic Effect of Fresh Nopal (Opuntia ficus-indica) in Low-Dose Streptozotocin-Induced Diabetic Rats Fed a High-Fat Diet.

Science.gov (United States)

Hwang, Seung Hwan; Kang, Il-Jun; Lim, Soon Sung

2017-01-01

The objective of the present study was to evaluate α -glucosidase inhibitory and antidiabetic effects of Nopal water extract (NPWE) and Nopal dry power (NADP) in low-dose streptozotocin- (STZ-) induced diabetic rats fed a high-fat diet (HFD). The type 2 diabetic rat model was induced by HFD and low-dose STZ. The rats were divided into four groups as follows: (1) nondiabetic rats fed a regular diet (RD-Control); (2) low-dose STZ-induced diabetic rats fed HFD (HF-STZ-Control); (3) low-dose STZ-induced diabetic rats fed HFD and supplemented with NPWE (100 mg/kg body weight, HF-STZ-NPWE); and (4) low-dose STZ-induced diabetic rats fed HFD and supplemented with comparison medication (rosiglitazone, 10 mg/kg, body weight, HF-STZ-Rosiglitazone). In results, NPWE and NADP had IC 50 values of 67.33 and 86.68  μ g/mL, both of which exhibit inhibitory activities but lower than that of acarbose (38.05  μ g/mL) while NPWE group significantly decreased blood glucose levels compared to control and NPDP group on glucose tolerance in the high-fat diet fed rats model ( P < 0.05). Also, the blood glucose levels of HR-STZ-NPWE group were significantly lower ( P < 0.05) than HR-STZ-Control group on low-dose STZ-induced diabetic rats fed HFD. Based on these findings, we suggested that NPWE could be considered for the prevention and/or treatment of blood glucose and a potential use as a dietary supplement.

The role of radiation types and dose in induced genomic instability

International Nuclear Information System (INIS)

Kadhim Munira, A.

2007-01-01

Complete text of publication follows. Genomic Instability (GI) is defined as long-term alterations induced by low-dose exposure to a variety of genotoxic agents in mammalian cells that act to increase the 'apparent' spontaneous mutation frequency.GI is a hallmark of tumorigenic progression and is observed in the progeny of irradiated and bystander cells as the delayed and stochastic appearance of de novo chromosomal aberrations, gene mutations and delayed lethal mutations both in vitro and in vivo. It occurs at a frequency several orders of magnitude greater than would be expected for mutation in a single gene, implying that GI is a multigenic phenomenon. The expression of GI can be influenced by genotype, cell type and radiation quality; however the underlying mechanisms are not fully understood. While several studies have demonstrated GI induction by high and low LET radiation, our work on human and mouse primary cell systems has shown significant differences in the capacity to induce GI and the spectrum of alterations depending on LET. These differences might be attributed to differences in radiation track structure, radiation dose and radiation exposure regime (distribution of hit and un hit cells). In this presentation I shall review the role of radiation quality; describe the possible mechanisms underlining the observed differences between radiation type and present results of experiments demonstrating that the dose of low LET radiation might be the most significant factor in determining the role of radiation type in the induction of GI.

Menadione-Induced Oxidative Stress Re-Shapes the Oxylipin Profile of Aspergillus flavus and Its Lifestyle.

Science.gov (United States)

Zaccaria, Marco; Ludovici, Matteo; Sanzani, Simona Marianna; Ippolito, Antonio; Cigliano, Riccardo Aiese; Sanseverino, Walter; Scarpari, Marzia; Scala, Valeria; Fanelli, Corrado; Reverberi, Massimo

2015-10-23

Aspergillus flavus is an efficient producer of mycotoxins, particularly aflatoxin B₁, probably the most hepatocarcinogenic naturally-occurring compound. Although the inducing agents of toxin synthesis are not unanimously identified, there is evidence that oxidative stress is one of the main actors in play. In our study, we use menadione, a quinone extensively implemented in studies on ROS response in animal cells, for causing stress to A. flavus. For uncovering the molecular determinants that drive A. flavus in challenging oxidative stress conditions, we have evaluated a wide spectrum of several different parameters, ranging from metabolic (ROS and oxylipin profile) to transcriptional analysis (RNA-seq). There emerges a scenario in which A. flavus activates several metabolic processes under oxidative stress conditions for limiting the ROS-associated detrimental effects, as well as for triggering adaptive and escape strategies.

Search for the lowest irradiation dose from literatures on radiation-induced bone tumor

Energy Technology Data Exchange (ETDEWEB)

Yoshizawa, Y; Kusama, T; Morimoto, K [Tokyo Univ. (Japan). Faculty of Medicine

1977-04-01

A survey of past case reports of bone tumor induced by external radiation was carried out with the main object of finding the lowest irradiation dose. Search of the literature published since 1922 revealed 262 cases of radiation-induced bone tumor. These patients, except a patient with occupational exposure, had received radiation for treatment. The primary conditions as object of radiation therapy were nonmalignan bone diseases such as tuberclosis, giant cell tumor, fibrous dysplasia and bone cyst, and extra-skeletal diseases such as retinoblastoma, breast cancer and uterus cancer. The ratio of male to female patients with radiation-induced bone tumor was 1:1.3. The age of the patient ranged between 5 and 98 years, with an average of 37.6 years. Skeletal distribution of radiation-induced bone tumor was as follows: 20% the frontal and face bones, 17% the femur, 10% the humerus, 9% the vertebral column, and 44% other. The lowest absorbed dose reported was 800 rads in patients irradiated for the treatment of bone disease, but 1800 rads in patients with extra-skeletal disease. The latent period ranged between 2 and 42 years, with an average of 11.7 years. The histopathological findings were as follows: 60% osteosarcoma, 25% fibrosarcoma, 7% chondrosarcoma, and 8% other.

MAGIK: a Monte Carlo system for computing induced residual activation dose rates

International Nuclear Information System (INIS)

Barish, J.; Gabriel, T.A.; Alsmiller, R.G. Jr.

1979-08-01

The photon dose rate from the induced activity produced by sustained bombardment of materials by neutrons and charged particles may present a significant radiation hazard. To minimize this hazard, the material configuration must be so designed that the photon dose rate decays to an acceptable level soon after the source beam is turned off. MAGIK calculates the time-independent photon dose rates that result from activities produced by nucleon-nucleus and meson-nucleus collisions over a wide range of energies. The system has been used both for high-energy accelerator studies and for fusion reactor studies. In the MAGIK system the lengthy photon transport calculations are carried out independent of time, and the time dependence is introduced in the final program, thereby permitting study of various operating scenarios with a minimum computing cost

Low-dose cadmium exposure exacerbates polyhexamethylene guanidine-induced lung fibrosis in mice.

Science.gov (United States)

Kim, Min-Seok; Kim, Sung-Hwan; Jeon, Doin; Kim, Hyeon-Young; Han, Jin-Young; Kim, Bumseok; Lee, Kyuhong

2018-01-01

Cadmium (Cd) is a toxic metal present in tobacco smoke, air, food, and water. Inhalation is an important route of Cd exposure, and lungs are one of the main target organs for metal-induced toxicity. Cd inhalation is associated with an increased risk of pulmonary diseases. The present study aimed to assess the effects of repeated exposure to low-dose Cd in a mouse model of polyhexamethylene guanidine (PHMG)-induced lung fibrosis. Mice were grouped into the following groups: vehicle control (VC), PHMG, cadmium chloride (CdCl 2 ), and PHMG + CdCl 2 . Animals in the PHMG group exhibited increased numbers of total cells and inflammatory cells in the bronchoalveolar lavage fluid (BALF) accompanied by inflammation and fibrosis in lung tissues. These parameters were exacerbated in mice in the PHMG + CdCl 2 group. In contrast, mice in the CdCl 2 group alone displayed only minimal inflammation in pulmonary tissue. Expression of inflammatory cytokines and fibrogenic mediators was significantly elevated in lungs of mice in the PHMG group compared with that VC. Further, expression of these cytokines and mediators was enhanced in pulmonary tissue in mice administered PHMG + CdCl 2 . Data demonstrate that repeated exposure to low-dose Cd may enhance the development of PHMG-induced pulmonary fibrosis.

Dose-dependent neuroprotective effect of enoxaparin on cold-induced traumatic brain injury.

Science.gov (United States)

Keskin, Ilknur; Gunal, M Yalcin; Ayturk, Nilufer; Kilic, Ulkan; Ozansoy, Mehmet; Kilic, Ertugrul

2017-05-01

Recent evidence exists that enoxaparin can reduce brain injury because of its anticoagulant activity. To investigate the potential therapeutic effect of enoxaparin on cold-induced traumatic brain injury, at 20 minutes after modeling, male BALB/c mouse models of cold-induced traumatic brain injury were intraperitoneally administered 3 and 10 mg/kg enoxaparin or isotonic saline solution. Twenty-four hours later, enoxaparin at 10 mg/kg greatly reduced infarct volume, decreased cell apoptosis in the cortex and obviously increased serum level of total antioxidant status. By contrast, administration of enoxaparin at 3 mg/kg did not lead to these changes. These findings suggest that enoxaparin exhibits neuroprotective effect on cold-induced traumatic brain injury in a dose-dependent manner.

Low dose radiation induced protein and its effect on expression of CD25 molecule in lymphocytes

International Nuclear Information System (INIS)

Lu Duicai; Su Liaoyuan

2001-01-01

Objective: To find the substantial basis for effects of low dose radiation, on development, extraction, and the biogical activity of the low-dose radiation-induced proteins, and the effects of LDR induced proteins on CD25 molecule expression of human lymphocytes. Methods: 1. Healthy Kumning male mice exposed to radiation of 226 Ra γ-rays at 5, 10 and 15 cGy respectively. The mice were killed 2 hours after exposure, the spleen cells were broken with ultrasonic energy and then ultra-centrifugalized at low temperature (4 degree C). The LDR-induced proteins were obtained in the supernatant solution. Then the changes of CD25 molecule was measured by flow cytometry (FCM) with immunofluorescence technique, which was used to reflect the effect of LDR induced proteins on CD25 molecule expression of human lymphocytes. Results: LDR induced proteins were obtained from spleen cells in mice exposed to 5-15 cGy whole body radiation. Conclusion: The expression of CD25 molecule of lymphocytes was increased significantly after use of LDR induced proteins. LDR induced proteins can enhance expression of CD25 molecule of lymphocytes slightly

Dose rate effect on the yield of radiation induced response with thermal fading

International Nuclear Information System (INIS)

Chernov, V.; Rogalev, B.; Barboza-Flores, M.

2005-01-01

A model describing the dependences of the accumulation of thermally unstable radiation induced defects on the dose and dose rate is proposed. The model directly takes into account the track nature of the ionizing radiation represented as accumulation processes of defects in tracks averaged over a crystal volume considering various degrees of overlapping in space and time. The accumulation of the defects in the tracks is phenomenologically described. General expressions are obtained that allows radiation yield simulation of defects involving known creation and transformation processes. The cases considered, of linear accumulation (constant increment of the defects in tracks) and accumulation with saturation (complete saturation of the defects in one track), lead to a set of linear dose dependences with saturation, which are routinely used in luminescence and ESR dating. The accumulation, with increase of sensitivity in regions overlapped by two or more tracks, gave a set of dose dependences, from linear-sublinear-linear-saturation, distinctive of quartz up to linear-supralinear-linear-saturation. It is shown that the effect of the dose rate on dose dependences is determined by a dimensionless parameter a=Pτ/D0, where P is the dose rate, τ is the defect lifetime and D0 is the track dose. At a-bar 1 the dose rate influences basically the accumulation of thermally unstable defects. In the reverse case the dose dependences did not seems to be influenced by the dose rate

High doses of bone morphogenetic protein 2 induce structurally abnormal bone and inflammation in vivo.

Science.gov (United States)

Zara, Janette N; Siu, Ronald K; Zhang, Xinli; Shen, Jia; Ngo, Richard; Lee, Min; Li, Weiming; Chiang, Michael; Chung, Jonguk; Kwak, Jinny; Wu, Benjamin M; Ting, Kang; Soo, Chia

2011-05-01

The major Food and Drug Association-approved osteoinductive factors in wide clinical use are bone morphogenetic proteins (BMPs). Although BMPs can promote robust bone formation, they also induce adverse clinical effects, including cyst-like bone formation and significant soft tissue swelling. In this study, we evaluated multiple BMP2 doses in a rat femoral segmental defect model and in a minimally traumatic rat femoral onlay model to determine its dose-dependent effects. Results of our femoral segmental defect model established a low BMP2 concentration range (5 and 10 μg/mL, total dose 0.375 and 0.75 μg in 75 μg total volume) unable to induce defect fusion, a mid-range BMP2 concentration range able to fuse the defect without adverse effects (30 μg/mL, total dose 2.25 μg in 75 μg total volume), and a high BMP2 concentration range (150, 300, and 600 μg/mL, total dose 11.25, 22.5, and 45 μg in 75 μg total volume) able to fuse the defect, but with formation of cyst-like bony shells filled with histologically confirmed adipose tissue. In addition, compared to control, 4 mg/mL BMP2 also induced significant tissue inflammatory infiltrates and exudates in the femoral onlay model that was accompanied by increased numbers of osteoclast-like cells at 3, 7, and 14 days. Overall, we consistently reproduced BMP2 side effects of cyst-like bone and soft tissue swelling using high BMP2 concentration approaching the typical human 1500 μg/mL.

Dose response of micronuclei induced by combination radiation of α-particles and γ-rays in human lymphoblast cells

Energy Technology Data Exchange (ETDEWEB)

Ren, Ruiping; He, Mingyuan; Dong, Chen; Xie, Yuexia; Ye, Shuang; Yuan, Dexiao [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China); Shao, Chunlin, E-mail: clshao@shmu.edu.cn [Institute of Radiation Medicine, Fudan University, No. 2094 Xie-Tu Road, Shanghai 200032 (China)

2013-01-15

Highlights: ► α-Particle induced MN had a biphasic dose–response followed by a bystander model. ► MN dose–response of α- and γ-combination IR was similar to that of α-particle. ► α-Particles followed by γ-rays yielded a synergistic effect on MN induction. ► Low dose γ-rays triggered antagonistic and adaptive responses against α-particle. - Abstract: Combination radiation is a real situation of both nuclear accident exposure and space radiation environment, but its biological dosimetry is still not established. This study investigated the dose–response of micronuclei (MN) induction in lymphocyte by irradiating HMy2.CIR lymphoblast cells with α-particles, γ-rays, and their combinations. Results showed that the dose–response of MN induced by γ-rays was well-fitted with the linear-quadratic model. But for α-particle irradiation, the MN induction had a biphasic phenomenon containing a low dose hypersensitivity characteristic and its dose response could be well-stimulated with a state vector model where radiation-induced bystander effect (RIBE) was involved. For the combination exposure, the dose response of MN was similar to that of α-irradiation. However, the yield of MN was closely related to the sequence of irradiations. When the cells were irradiated with α-particles at first and then γ-rays, a synergistic effect of MN induction was observed. But when the cells were irradiated with γ-rays followed by α-particles, an antagonistic effect of MN was observed in the low dose range although this combination radiation also yielded a synergistic effect at high doses. When the interval between two irradiations was extended to 4 h, a cross-adaptive response against the other irradiation was induced by a low dose of γ-rays but not α-particles.

Inhibitory effects of prior low-dose X-ray irradiation on carbon tetrachloride-induced hepatopathy in acatalasemic mice

International Nuclear Information System (INIS)

Yamaoka, Kiyonori; Kataoka, Takahiro; Taguchi, Takehito; Wang, Da-Hong; Mori, Shuji; Hanamoto, Katsumi; Kira, Shohei; Nomura, Takaharu

2004-01-01

The catalase activities in blood and organs of the acatalasemic (C3H/AnLCs b Cs b ) mouse of C3H strain are lower than those of the normal (C3H/AnLCs a Cs a ) mouse. We examined the effects of prior low-dose (0.5 Gy) X-ray irradiation, which reduced the oxidative damage under carbon tetrachloride-induced hepatopathy in the acatalasemic or normal mice. The acatalasemic mice showed a significantly lower catalase activity and a significantly higher glutathione peroxidase activity compared with those in the normal mice. Moreover, low-dose irradiation increased the catalase activity in the acatalasemic mouse liver to a level similar to that of the normal mouse liver. Pathological examinations and analyses of blood glutamic oxaloacetic and glutamic pyruvic transaminase activity and lipid peroxide levels showed that carbon tetrachloride induced hepatopathy was inhibited by low-dose irradiation. These findings may indicate that the free radical reaction induced by the lack of catalase and the administration of carbon tetrachloride is more properly neutralized by high glutathione peroxidase activity and low-dose irradiation in the acatalasemic mouse liver. (author)

A UV-Induced Genetic Network Links the RSC Complex to Nucleotide Excision Repair and Shows Dose-Dependent Rewiring

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Rohith Srivas

2013-12-01

Full Text Available Efficient repair of UV-induced DNA damage requires the precise coordination of nucleotide excision repair (NER with numerous other biological processes. To map this crosstalk, we generated a differential genetic interaction map centered on quantitative growth measurements of >45,000 double mutants before and after different doses of UV radiation. Integration of genetic data with physical interaction networks identified a global map of 89 UV-induced functional interactions among 62 protein complexes, including a number of links between the RSC complex and several NER factors. We show that RSC is recruited to both silenced and transcribed loci following UV damage where it facilitates efficient repair by promoting nucleosome remodeling. Finally, a comparison of the response to high versus low levels of UV shows that the degree of genetic rewiring correlates with dose of UV and reveals a network of dose-specific interactions. This study makes available a large resource of UV-induced interactions, and it illustrates a methodology for identifying dose-dependent interactions based on quantitative shifts in genetic networks.

Evaluation of the repeated-dose liver micronucleus assay using N-nitrosomorpholine in young adult rats: report on collaborative study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Japanese Environmental Mutagen Society (JEMS)-Mammalian Mutagenicity Study (MMS) Group.

Science.gov (United States)

Hayashi, Aya; Kosaka, Mizuki; Kimura, Aoi; Wako, Yumi; Kawasako, Kazufumi; Hamada, Shuichi

2015-03-01

The present study was conducted to evaluate the suitability of a repeated-dose liver micronucleus (LMN) assay in young adult rats as a collaborative study by the Mammalian mutagenicity study (MMS) group. All procedures were performed in accordance with the standard protocols of the MMS Group. Six-week-old male Crl:CD(SD) rats (5 animals/group) received oral doses of the hepatocarcinogen N-nitrosomorpholine (NMOR) at 0 (control), 5, 10, and 30mg/kg/day (10mL/kg) for 14 days. Control animals received vehicle (water). Hepatocytes were collected from the liver 24h after the last dose, and the number of micronucleated hepatocytes (MNHEPs) was determined by microscopy. The number of micronucleated immature erythrocytes (MNIMEs) in the femoral bone marrow was also determined. The liver was examined using histopathologic methods after formalin fixation. The results showed statistically significant and dose-dependent increases in the number of MNHEPs in the liver at doses of 10mg/kg and greater when compared with the vehicle control. However, no significant increase was noted in the number of MNIMEs in the bone marrow at doses of up to 30mg/kg. Histopathology of the liver revealed hypertrophy and single cell necrosis of hepatocytes at doses of 5mg/kg and above. These results showed that the induction of micronuclei by NMOR was detected by the repeated-dose LMN assay, but not by the repeated-dose bone marrow micronucleus assay. Copyright © 2014 Elsevier B.V. All rights reserved.

Dose-response relationship for chromosomal aberrations induced in human lymphocytes by 18 MeV electron beam irradiation

International Nuclear Information System (INIS)

Lashin, E.A.; Elaasar, E.M.; Moustafa, H.F.; Bakir, Y.Y.; Al Zenki, S.D.

1990-01-01

Dose response curves for lymphocyte chromosome aberration frequencies using X- and gamma radiation became an important and reliable indicator as biological dosimeter especially in radiation accidents and occupational over exposures. Nowadays electron beam therapy is frequently used for their advantages in cases of tumours under or near to the body surface. Dose-response curves for these electron beams are rarely published. Human peripheral blood lymphocytes were in vitro irradiated with various low and high doses (0.1 Gy to 4.9 Gy) of 18 MeV electron beams to utilize such a dose-response curve using chromosomal aberration frequencies as a biological indicator. Then we compared the biological curve with physically obtained curves normally used in planning for radiotherapy treatment. It is interesting to find a significant difference between both of them. The biological curve is generally higher in value and the aberrations induced by 93% of a dose is significantly higher and deeper in site than those aberrations induced by the 100% dose calculated physically. If the above observation is confirmed by detailed studies, it would be of importance to the radiotherapist to plan for isodose curves according to biological determinations. (author)

Ultraviolet Radiation Induces Dose-Dependent Pigment Dispersion in Crustacean Chromatophores

OpenAIRE

Gouveia, Glauce Ribeiro; Lopes, Thaís Martins; Neves, Carla Amorim; Nery, Luiz Eduardo Maia; Trindade, Gilma Santos

2004-01-01

Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm2 for UVA and 2.15 J/cm2 for UVB. Maximal response was achieved with 10.0 J/cm...

cDNA cloning and transcriptional controlling of a novel low dose radiation-induced gene and its function analysis

International Nuclear Information System (INIS)

Zhou Pingkun; Sui Jianli

2002-01-01

Objective: To clone a novel low dose radiation-induced gene (LRIGx) and study its function as well as its transcriptional changes after irradiation. Methods: Its cDNA was obtained by DDRT-PCR and RACE techniques. Northern blot hybridization was used to investigate the gene transcription. Bioinformatics was employed to analysis structure and function of this gene. Results: LRIGx cDNA was cloned. The sequence of LRIGx was identical to a DNA clone located in human chromosome 20 q 11.2-12 Bioinformatics analysis predicted an encoded protein with a conserved helicase domain. Northern analysis revealed a ∼8.5 kb transcript which was induced after 0.2 Gy as well as 0.02 Gy irradiation, and the transcript level was increased 5 times at 4 h after 0.2 Gy irradiation. The induced level of LRIGx transcript by 2.0 Gy high dose was lower than by 0.2 Gy. Conclusion: A novel low dose radiation-induced gene has been cloned. It encodes a protein with a conserved helicase domain that could involve in DNA metabolism in the cellular process of radiation response

Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study

DEFF Research Database (Denmark)

Sorgenfrei, Iben F; Norrild, Kathrine; Larsen, Per Bo

2006-01-01

Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block.......Sugammadex (Org 25969) forms a complex with steroidal neuromuscular blocking agents, thereby reversing neuromuscular block. This study investigated the dose-response relation, safety, and pharmacokinetics of sugammadex to reverse rocuronium-induced block....

Low dose β-emitter source induces sexual reproduction instead of fragmentation in an earthworm, Enchytraeus japonensis

International Nuclear Information System (INIS)

Miyachi, Yukihisa; Kanao, Tomoko; Okamoto, Takehito

2005-01-01

We examined whether background radiation, or radiation at a slightly higher level, plays a role in the reproduction of a terrestrial earthworm. Enchytraeus japonensis a recently described terrestrial oligochaete, reproduces asexually by fragmentation and subsequent regeneration. Following radiation exposure in which the worms were subjected to a 32 P β-emitter source at 15 times the background dose rate (4.5 μGy/h), a statistically significant decrease in the number of fragmentations was observed as compared with the sham controls. At that time, in a stained preparation with haematoxylin and eosin (HE), sexual reproduction occurred instead of asexual fragmentation, and mature oocytes were observed in the body of grown worms. However, increasing the radiation dose rate by 30 μGy/h resulted in the complete disappearance of the radiation-induced effects, i.e., fragmentation again occurred after 14 h. The results of this study indicate that a lower dose of radiation may be essential to achieve sexual reproduction, inducing an inhibition of fragmentation (asexual reproduction), but at higher, more cytotoxic doses of radiation these effects are negated

Benchmark studies of induced radioactivity and remanent dose rates produced in LHC materials

International Nuclear Information System (INIS)

Brugger, M.; Mayer, S.; Roesler, S.; Ulrici, L.; Khater, H.; Prinz, A.; Vincke, H.

2005-01-01

Samples of materials that will be used for elements of the LHC machine as well as for shielding and construction components were irradiated in the stray radiation field of the CERN-EU high-energy Reference Field facility. The materials included various types of steel, copper, titanium, concrete and marble as well as light materials such as carbon composites and boron nitride. Emphasis was put on an accurate recording of the irradiation conditions, such as irradiation profile and intensity, and on a detailed determination of the elemental composition of the samples. After the irradiation, the specific activity induced in the samples as well as the remanent dose rate were measured at different cooling times ranging from about 20 minutes to two months. Furthermore, the irradiation experiment was simulated using the FLUKA Monte Carlo code and specific activities. In addition, dose rates were calculated. The latter was based on a new method simulating the production of various isotopes and the electromagnetic cascade induced by radioactive decay at a certain cooling time. In general, solid agreement was found, which engenders confidence in the predictive power of the applied codes and tools for the estimation of the radioactive nuclide inventory of the LHC machine as well as the calculation of remanent doses to personnel during interventions. (authors)

"Interaction of different doses of Aspartame with Morphine-induced antinociception in the presence of MK-801, a NMDA antagonist "

Directory of Open Access Journals (Sweden)

Abdollahi M

2002-07-01

Full Text Available This study was designed to investigate the relative role of sweetness and comparative effects of different taste sensation of the non - caloric sweetener , aspartame on pain and its interaction with MK - 80] as a non - selective MMDA antagonist by formalin - test in mice. The formalin - test was chosen because it measures the response to a long - lasting nociceptive stimulus and closely resembles to the clinical pain. Morphine induced a dose dependent antinociception in the early and late phases of formalin test. Twelve days pretreatment of animals by aspartame ( 0.08% , 0.16% , 0.32% significantly potentiated morphine - induced (1.5-9 mg/kg analgesia in the early phase but significantly antagonized its analgesic effect in the late phase, dose dependently. Aspartame (0.16% alone showed a reduction in pain response . Naloxone (0.4 mg/kg significantly antagonized the antinociceptive effect of morphine in the presence of aspartame (0-0.32% in the early phase. Increasing the dose of aspartame decreased effects of naloxone. MK-801 (0.1 mg/kg as an N- Methyl - D - Aspartate (NMDA antagonist significantly potentiated the effect of aspartame on morphine - induced antinociception in the early phase. In the late phase, naloxone (0.4 mg/kg increased pain response but MK- 801 (0.1 mg/kg induced anti-inflammatory effect significantly. Treatment of animals with MK- 801 alone, significantly induced analgesia in both phases of formalin - test. This effect was potentiated with aspartame dose - dependently. Possible interaction of aspartame with NMDA receptors and its role to facilitate endogenous opioid system are proposed mechanisms of aspartame in modulating morphine - induced antinociception. Furthermore, the resulting association between morphine and aspartame chronic consumption may be explained as an interactive action rather than simple dose combination of both drugs.

Neuroprotection and mechanisms of atractylenolide III in preventing learning and memory impairment induced by chronic high-dose homocysteine administration in rats.

Science.gov (United States)

Zhao, H; Ji, Z-H; Liu, C; Yu, X-Y

2015-04-02

Studies demonstrated that chronic high-dose homocysteine administration induced learning and memory impairment in animals. Atractylenolide III (Aen-III), a neuroprotective constituent of Atractylodis macrocephalae Koidz, was isolated in our previous study. In this study, we investigated potential benefits of Aen-III in preventing learning and memory impairment following chronic high-dose homocysteine administration in rats. Results showed that administration of Aen-III significantly ameliorated learning and memory impairment induced by chronic high-dose homocysteine administration in rats, decreased homocysteine-induced reactive oxygen species (ROS) formation and restored homocysteine-induced decrease of phosphorylated protein kinase C expression level. Moreover, Aen-III protected primary cultured neurons from apoptotic death induced by homocysteine treatment. This study provides the first evidence for the neuroprotective effect of Aen-III in preventing learning and impairment induced by chronic administration of homocysteine. Aen-III may have therapeutic potential in treating homocysteine-mediated cognitive impairment and neuronal injury. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Radiation-induced rectal complications are not influenced by age: a dose fractionation study in the rat.

Science.gov (United States)

van den Aardweg, Gerard J M J; Olofsen-van Acht, Manouk J J; van Hooije, Christel M C; Levendag, Peter C

2003-05-01

Radiation-induced complications of the rectum are an important dose-limiting factor in radiotherapy of pelvic malignancies. In general, animal studies demonstrated no differences in acute and late normal tissue toxicity with age, but little is known about rectal complications in relation to age. For this purpose, an extensive histological and dose fractionation study was carried out on the rectum of young (12 weeks) and older (77-80 weeks) rats. In this paper, the results of dose fractionation are presented in relation to age at the time of irradiation. Young and older animals were irradiated with single and fractionated doses. After irradiation, rectal complications could lead to occlusion and stenosis, eventually resulting in the clinical symptoms of a megacolon and a possible fistula. For each dose group, cumulative survival rates were obtained with Kaplan-Meier analysis, from which dose-effect curves and the associated LD(50) values for a megacolon/fistula were calculated. The majority of responders died between 8 and 24 weeks after irradiation, irrespective of age. For both age groups, only the fractionation data showed a reduction in the mean latency with increasing dose. In the older age group, 39% of the responders developed a fistula compared to 26% for the younger animals. The LD(50) values increased from around 30 Gy after single doses to nearly 65 Gy after 10 fractions. The increases in LD(50) values with the number of fractions were independent of the age of the rats. For each of the dose fractionation schedules, log-rank testing indicated no significant differences in cumulative survival rates between younger and older animals (P > 0.10). The high alpha/beta ratios obtained for both the young and older animals strongly suggested that the late rectal complications were a consequence of early epithelial injury. Associated histological findings indicated that blood vessel damage, which was already evident at a high incidence at 4 weeks after irradiation

Dose dependency of time of onset of radiation-induced growth hormone deficiency

International Nuclear Information System (INIS)

Clayton, P.E.; Shalet, S.M.

1991-01-01

Growth hormone (GH) secretion during insulin-induced hypoglycemia was assessed on 133 occasions in 82 survivors of childhood malignant disease. All had received cranial irradiation with a dose range to the hypothalamic-pituitary axis of 27 to 47.5 Gy (estimated by a schedule of 16 fractions over 3 weeks) and had been tested on one or more occasions between 0.2 and 18.9 years after treatment. Results of one third of the GH tests were defined as normal (GH peak response, greater than 15 mU/L) within the first 5 years, in comparison with 16% after 5 years. Stepwise multiple linear regression analysis showed that dose (p = 0.007) and time from irradiation (p = 0.03), but not age at therapy, had a significant influence on peak GH responses. The late incidence of GH deficiency was similar over the whole dose range (4 of 26 GH test results normal for less than 30 Gy and 4 of 25 normal for greater than or equal to 30 Gy after 5 years), but the speed of onset over the first years was dependent on dose. We conclude that the requirement for GH replacement therapy and the timing of its introduction will be influenced by the dose of irradiation received by the hypothalamic-pituitary axis

Single Low-Dose Radiation Induced Regulation of Keratinocyte Differentiation in Calcium-Induced HaCaT Cells

Science.gov (United States)

Hahn, Hyung Jin; Youn, Hae Jeong; Cha, Hwa Jun; Kim, Karam; An, Sungkwan

2016-01-01

Background We are continually exposed to low-dose radiation (LDR) in the range 0.1 Gy from natural sources, medical devices, nuclear energy plants, and other industrial sources of ionizing radiation. There are three models for the biological mechanism of LDR: the linear no-threshold model, the hormetic model, and the threshold model. Objective We used keratinocytes as a model system to investigate the molecular genetic effects of LDR on epidermal cell differentiation. Methods To identify keratinocyte differentiation, we performed western blots using a specific antibody for involucrin, which is a precursor protein of the keratinocyte cornified envelope and a marker for keratinocyte terminal differentiation. We also performed quantitative polymerase chain reaction. We examined whether LDR induces changes in involucrin messenger RNA (mRNA) and protein levels in calcium-induced keratinocyte differentiation. Results Exposure of HaCaT cells to LDR (0.1 Gy) induced p21 expression. p21 is a key regulator that induces growth arrest and represses stemness, which accelerates keratinocyte differentiation. We correlated involucrin expression with keratinocyte differentiation, and examined the effects of LDR on involucrin levels and keratinocyte development. LDR significantly increased involucrin mRNA and protein levels during calcium-induced keratinocyte differentiation. Conclusion These studies provide new evidence for the biological role of LDR, and identify the potential to utilize LDR to regulate or induce keratinocyte differentiation. PMID:27489424

Menadione-Induced Oxidative Stress Re-Shapes the Oxylipin Profile of Aspergillus flavus and Its Lifestyle

Science.gov (United States)

Zaccaria, Marco; Ludovici, Matteo; Sanzani, Simona Marianna; Ippolito, Antonio; Aiese Cigliano, Riccardo; Sanseverino, Walter; Scarpari, Marzia; Scala, Valeria; Fanelli, Corrado; Reverberi, Massimo

2015-01-01

Aspergillus flavus is an efficient producer of mycotoxins, particularly aflatoxin B1, probably the most hepatocarcinogenic naturally-occurring compound. Although the inducing agents of toxin synthesis are not unanimously identified, there is evidence that oxidative stress is one of the main actors in play. In our study, we use menadione, a quinone extensively implemented in studies on ROS response in animal cells, for causing stress to A. flavus. For uncovering the molecular determinants that drive A. flavus in challenging oxidative stress conditions, we have evaluated a wide spectrum of several different parameters, ranging from metabolic (ROS and oxylipin profile) to transcriptional analysis (RNA-seq). There emerges a scenario in which A. flavus activates several metabolic processes under oxidative stress conditions for limiting the ROS-associated detrimental effects, as well as for triggering adaptive and escape strategies. PMID:26512693

Menadione-Induced Oxidative Stress Re-Shapes the Oxylipin Profile of Aspergillus flavus and Its Lifestyle

Directory of Open Access Journals (Sweden)

Marco Zaccaria

2015-10-01

Full Text Available Aspergillus flavus is an efficient producer of mycotoxins, particularly aflatoxin B1, probably the most hepatocarcinogenic naturally-occurring compound. Although the inducing agents of toxin synthesis are not unanimously identified, there is evidence that oxidative stress is one of the main actors in play. In our study, we use menadione, a quinone extensively implemented in studies on ROS response in animal cells, for causing stress to A. flavus. For uncovering the molecular determinants that drive A. flavus in challenging oxidative stress conditions, we have evaluated a wide spectrum of several different parameters, ranging from metabolic (ROS and oxylipin profile to transcriptional analysis (RNA-seq. There emerges a scenario in which A. flavus activates several metabolic processes under oxidative stress conditions for limiting the ROS-associated detrimental effects, as well as for triggering adaptive and escape strategies.

Search for the lowest irradiation dose from literatures on radiation-induced cancer in gastrointestinal tract

Energy Technology Data Exchange (ETDEWEB)

Yoshizawa, Y; Kusama, T [Tokyo Univ. (Japan). Faculty of Medicine

1976-05-01

A survey of past case reports about radiation-induced cancer in the gastrointestinal tract was carried out with the main object of finding the lowest irradiation dose. Search of the literature published since 1923 revealed 80 cases of radiation-induced large intestine cancer and one case of stomach cancer. The cases of radiation-induced cancer in the large intestine had received radiation for the treatment of non-malignant conditions, fibroma, ovarial cyste, myoma, endometritis and duodenal ulcer. The lowest irradiation dose was estimated at 460 rads. Adenocarcinoma was the histopathological finding in all cases of radiation-induced cancer in the caecum, colon and rectum, and squamous cell carcinoma in the cases of anal cancer. The latent period ranged from 1 to 31 years, with the average of 13.6 years. There were some reports of statistical studies of radiation-induced stomach cancer. Three groups were the subjects of these studies. The first group was composed of atomic bomb survivors, the second of patients who had undergone radiation treatment for ankylosing spondilitis, and the third of duodenal ulcer patients subjected to radiation treatment for the purpose of suppressing gastric acid secretion. These statistical studies showed no significant increase of the incidence of stomach cancer in the irradiated groups.

Search for the lowest irradiation dose from literatures on radiation-induced cancer in gastrointestinal tract

International Nuclear Information System (INIS)

Yoshizawa, Yasuo; Kusama, Tomoko

1976-01-01

A survey of past case reports about radiation-induced cancer in the gastrointestinal tract was carried out with the main object of finding the lowest irradiation dose. Search of the literature published since 1923 revealed 80 cases of radiation-induced large intestine cancer and one case of stomach cancer. The cases of radiation-induced cancer in the large intestine had received radiation for the treatment of non-malignant conditions, fibroma, ovarial cyste, myoma, endometritis and duodenal ulcer. The lowest irradiation dose was estimated at 460 rads. Adenocarcinoma was the histopathological finding in all cases of radiation-induced cancer in the caecum, colon and rectum, and squamous cell carcinoma in the cases of anal cancer. The latent period ranged from 1 to 31 years, with the average of 13.6 years. There were some reports of statistical studies of radiation-induced stomach cancer. Three groups were the subjects of these studies. The first group was composed of atomic bomb survivors, the second of patients who had undergone radiation treatment for ankylosing spondilitis, and the third of duodenal ulcer patients subjected to radiation treatment for the purpose of suppressing gastric acid secretion. These statistical studies showed no significant increase of the incidence of stomach cancer in the irradiated groups. (auth.)

Low-dose ionizing radiation alleviates Aβ42-induced defective phenotypes in Drosophila Alzheimer's disease models

Energy Technology Data Exchange (ETDEWEB)

Hwang, SooJin; Jeong, Hae Min; Nam, Seon Young [Low-dose Radiation Research Team, Radiation Health Institute, Korea Hydro & Nuclear Power Co. Ltd., Daejeon (Korea, Republic of)

2017-04-15

Alzheimer's disease (AD) is the most common neurodegenerative disease that is characterized by amyloid plaques, progressive neuronal loss, and gradual deterioration of memory. Amyloid imaging using positron emission tomography (PET) radiotracers have been developed and approved for clinical use in the evaluation of suspected neurodegenerative disease, including AD. Particularly, previous studies involving low-dose ionizing radiation on Aβ 42-treated mouse hippocampal neurons have suggested a potential role for low-dose ionizing radiation in the treatment of AD. However, associated in vivo studies involving the therapy effects of low-dose ionizing radiation on AD are still insufficient. As a powerful cell biological system, Drosophila AD models have been generated and established a useful model organism for study on the etiology of human AD. In this study, we investigated the hormesis effects of low-dose ionizing radiation on Drosophila AD models. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation. Our results suggest that low-dose ionizing radiation have the beneficial effects on not only the Aβ42-induced developmental defective phenotypes but also motor defects in Drosophila AD models. These results might be due to a regulation of apoptosis, and provide insight into the hormesis effects of low-dose ionizing radiation.

Chronic UVA (365-nm) irradiation induced scratching in hairless mice: dose-time dependency and the effect of ketanserin

International Nuclear Information System (INIS)

Laat, J.M.T. de; Groenendijk, M.; Vloten, W.A. van; Gruijl, F.R. de; Seite, S.

1997-01-01

In a study on the dose-response relationship for longwave UVA (UVA1; 340-400 nm) carcinogenesis in hairless mice scratch marks appeared after months of daily exposure as an unwanted side effect. Tumor induction in the highest of the 4 tested dose groups (receiving a daily dose of 430 kJ/m 2 of 365-nm radiation) could not be determined because extensive scarification occurred prior to the development of any tumors. The induction of scratch marks could be scored and quantified in all 4 dose groups tested. The UVA1 dose-dependencies for the induction of tumors and scratch marks were compared. We found that the induction of scratch marks depended mainly on the cumulative UVA1 exposure, whereas tumor induction showed a lesser dose-dependency. An attempt was made to prevent the apparent pruritogenic effect of UVA1 irradiation and to understand its mechanism. The influence of ketanserin, a serotonin/histamine antagonist, on the UVA1 induction of scratch marks was tested in groups of 8 mice daily irradiated with 430 kJ/m 2 . No difference was found between treated and untreated animals. Histological examination of skin biopsies from irradiated mice from the 430-kJ/m 2 dose group from the UVA1 carcinogenic experiment, showed no changes in numbers of mast cells or other inflammatory features when compared to skin biopsies from unirradiated control mice. This indicated that UVA1-induced scratching is not mediated through mast cell release of serotonin and/or histamine. An adequate therapeutic treatment which can prevent UVA1-induced scratching would enable us to test tumor induction with UVA1 over a larger dose range, and may provide additional insight in how this radiation damages the skin. It remains conjectural whether there exists and analogous UVA-induced pruritus in human skin. (au)

Radiation induced skeletal changes in beagle: dose rates, dose, and age effect analysis from 226Ra

International Nuclear Information System (INIS)

Momeni, M.H.; Williams, J.R.; Rosenblatt, L.S.

1976-01-01

Radiation-induced skeletal injury (E) and the rate of skeletal injury were studied as a function of time and dose in beagles administered 226 Ra Cl 2 in eight semimonthly iv injections starting at 2, 4, or 14 months of age. Skeletal changes were evaluated with a radiographic x-ray scoring system in 20 skeletal regions; each region was scored on a 0 to 6 scale. Bone changes in six regions of humeri were qualitatively analyzed for comparison with total skeletal changes. Skeletal changes were classified by endosteal or periosteal cortical sclerosis and thickening, fractures, osteolytic lesions, and trabecular coarsening

Galactic cosmic ray-induced radiation dose on terrestrial exoplanets.

Science.gov (United States)

Atri, Dimitra; Hariharan, B; Grießmeier, Jean-Mathias

2013-10-01

This past decade has seen tremendous advancements in the study of extrasolar planets. Observations are now made with increasing sophistication from both ground- and space-based instruments, and exoplanets are characterized with increasing precision. There is a class of particularly interesting exoplanets that reside in the habitable zone, which is defined as the area around a star where the planet is capable of supporting liquid water on its surface. Planetary systems around M dwarfs are considered to be prime candidates to search for life beyond the Solar System. Such planets are likely to be tidally locked and have close-in habitable zones. Theoretical calculations also suggest that close-in exoplanets are more likely to have weaker planetary magnetic fields, especially in the case of super-Earths. Such exoplanets are subjected to a high flux of galactic cosmic rays (GCRs) due to their weak magnetic moments. GCRs are energetic particles of astrophysical origin that strike the planetary atmosphere and produce secondary particles, including muons, which are highly penetrating. Some of these particles reach the planetary surface and contribute to the radiation dose. Along with the magnetic field, another factor governing the radiation dose is the depth of the planetary atmosphere. The higher the depth of the planetary atmosphere, the lower the flux of secondary particles will be on the surface. If the secondary particles are energetic enough, and their flux is sufficiently high, the radiation from muons can also impact the subsurface regions, such as in the case of Mars. If the radiation dose is too high, the chances of sustaining a long-term biosphere on the planet are very low. We have examined the dependence of the GCR-induced radiation dose on the strength of the planetary magnetic field and its atmospheric depth, and found that the latter is the decisive factor for the protection of a planetary biosphere.

Determination of dose ranges of gamma rays to induce specific changes in three ornamental species

International Nuclear Information System (INIS)

Gonzalez J, J.

2011-11-01

In order to confirming the possibility of to settle a dose range that takes place directly and not at random, a specific effect independently of the species that is were produced several similar organisms to three ornamental species took place via meristems cultivation: Petunia hybrid, Impatiens walleriana and Sprekelia formosissima, same that were irradiated in an irradiator Gamma cell 220, to different dose: 0, 3.5, 5.0, 7.5, 10, 12.5, 15, 17.5 and 20 Gy. Later on, of the plants treated via in vitro the subsequent generations were obtained until the M 4 . To determine the DL 50 and the possible good doses, the survival parameters, development, morphogenesis and height were evaluated during 8 weeks, interpreting based on them, the possible physiologic and genetic alterations induced by the radiation. The established DL 50 were: 7.5 Gy (Petunia), 19.0 Gy (Impatiens) and 12.0 Gy (Sprekelia). Based on the DL 50 of each species, a range of coincident dose settled down that produces a similar effect in the three species: a range of DL 23 to the DL 50 induces and alteration in the cytokinins production affecting directly in the leaves number, buds and plants taken place by meristem, also a range of DL 32 - DL 50 impacts in the auxins production altering to the radicule system. However, when being superimposed the dose is considered that the investigation should continue. (Author)

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

International Nuclear Information System (INIS)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo

2005-01-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

High-dose radiation-induced meningioma following prophylactic cranial irradiation for acute lymphoblastic leukaemia

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Ryosuke; Nikaido, Yuji; Yamada, Tomonori; Mishima, Hideaki; Tamaki, Ryo [National Hospital Organization Osaka Minami Medical Center, Kawachinagano (Japan)

2005-03-01

A 12 year-old girl was treated with prophylactic cranial irradiation for acute lymphoblastic leukaemia (ALL). At the age of 39, she was admitted to our hospital for status epilepticus. Computed tomography demonstrated two, enhancing bilateral sided intracranial tumors. After surgery, this patient presented meningiomas which histologically, were of the meningothelial type. The high cure rate in childhood ALL, attributable to aggressive chemotherapy and prophylactic cranial irradiation, is capable of inducing secondary brain tumor. Twelve cases of high-dose radiation-induced meningioma following ALL are also reviewed. (author)

LET and dose rate effect on radiation-induced copolymerization of maleimide with styrene in 2-propanol solution

Energy Technology Data Exchange (ETDEWEB)

Nakagawa, Seiko, E-mail: Nakagawa.Seiko@iri-tokyo.jp [Tokyo Metropolitan Industrial Technology Research Institute, 2-4-10 Aoumi, Koto-ku, Tokyo 135-0064 (Japan); Taguchi, Mitsumasa; Kimura, Atsushi [Environmental Radiation Processing Group, Environment and Industrial Materials Research Division, Quantum Beam Science Directorate, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma 370-1292 (Japan)

2011-11-15

N{sub 2}-saturated 2-propanol solutions containing styrene and maleimide were irradiated by electron, proton, He and C-ion beams. The styrene-maleimide copolymer was produced by radical polymerization induced during irradiation. The effects of the radical distribution, which depends on the LET or dose rate, on the molecular weight and the polymer yield were discussed. - Highlights: > Maleimide with styrene in N{sub 2}-saturated 2-propanol was irradiated by electron and heavy ions. > LET and dose rate effects of radical polymerization induced by irradiation were studied. > Results have shown the relation between radical distribution and efficiency of polymerization.

From personnel dose to personal dose

International Nuclear Information System (INIS)

Hoefert, M.; Raffnsoe, R.C.; Tuyn, J.W.N.; Wittekind, D.

1985-01-01

From following the development of personnel doses at CERN over the past six years it has become evident that work in areas of induced radioactivity is the principal cause of exposure. The results of photon dose measurements free-in-air and around a phantom are presented and discussed in the light of new quantities in individual monitoring. The importance of these results, with respect to the practical situation, is discussed and the problem of phantom size is mentioned. Finally, the results of dose measurements in the phantom are presented, since such information is important in cases where it becomes necessary to transform personnel doses into personal doses. (author)

Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

Science.gov (United States)

Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

2007-03-05

Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

Low-dose acute vanillin is beneficial against harmaline-induced tremors in rats.

Science.gov (United States)

Abdulrahman, Al Asmari; Faisal, Kunnathodi; Meshref, Ali Al Amri; Arshaduddin, Mohammed

2017-03-01

To study the effect of pretreatment with low doses of vanillin, a flavoring agent used as a food additive, on harmaline-induced tremor in rats. Sprague Dawley rats (110 ± 5 g) were divided into groups of six animals each. Vanillin (6.25 mg, 12.5 mg, and 25 mg/kg) was administered by gavage to different groups of rats, 30 minutes before the induction of tremor. Harmaline (10 mg/kg, i.p.) was used for the induction of tremor. The latency of onset, duration, tremor intensity, tremor index, and spontaneous locomotor activity were recorded. A separate batch of animals was used for the determination of serotonin (5HT) and 5 hydroxyindole acetic acid (5HIAA) levels in the brain. Harmaline treatment resulted in characteristic tremor that lasted for more than 2 hours and decreased the locomotor activity of rats. Pre-treatment with vanillin significantly reduced the duration, intensity, and tremor index of harmaline-treated animals. Vanillin treatment also significantly attenuated harmaline-induced decrease in the locomotor activity. An increase in 5HT levels and the changes in 5HIAA/5HT ratio observed in harmaline treated rats were significantly corrected in vanillin pretreated animals. Vanillin in low doses reduces harmaline-induced tremor in rats, probably through its modulating effect on serotonin levels in the brain. These findings suggest a beneficial effect of vanillin in essential tremor.

The Effects of Pretreatment with Various Doses of L-Arginine on Cisplatin-Induced Nephropathy of Male Rats

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B Rasoulian

2016-09-01

Full Text Available Introduction: Cisplatin is a widely used anti-cancer drug, which its application is limited by nephrotoxicity. In this study, the effect of pretreatment with different l-arginine doses on Cisplatin-induced renal functional injury was investigated. Methods: 63 male rats were divided into 7 groups: In groups 3, 4, 5 and 6, 60 min before the Cisplatin injection (5mg/kg; L-Arginine with doses of 50,100,200 or 400mg/kg was injected, respectively. In group7, normal saline was injected before Cisplatin administration. In groups 1 and 2, normal saline was injected instead of Cisplatin. In group 2, 60min before normal saline injection, 400mg/kg L-Arginine was administered and in group1, instead of L-arginine, normal saline was injected too. Injections were intraperitoneal. 72h after Cisplatin injection, blood sampling and plasma separation were done. Urine sample was collected 24 hours before blood sampling by metabolic cage. The mean of plasma urea and creatinine levels and creatinine clearance (ml/day.kg and fractional excretion of Na (FENa, % were compared among different groups as renal functional parameters. Results: In comparison to group 7, L-arginine injection in a dose of 400mg/kg led to significant amelioration of all parameters. 200 mg/kg L-arginine administration led to significant decrease in plasma urea level and FENa. 100mg/kg L-arginine caused significant improvement in fractional excretion of sodium. L-arginine injection with 50mg/kg dose, significantly ameliorate all renal function tests instead of creatinine clearance. Conclusion: Pretreatment with L-arginine administration with 400 or 50 mg/kg doses, respectively, had the highest effect on reducing Cisplatin-induced nephropathy. L-arginine injection with intermediate doses i.e. 200 or 100 mg/kg had less effect in reducing Cisplatin-induced nephropathy and it needs more investigations.

Tests of the linearity assumption in the dose-effect relationship for radiation-induced cancer

International Nuclear Information System (INIS)

Cohen, A.F.; Cohen, B.L.

1980-01-01

The validity of the BEIR linear extrapolation to low doses of the dose-effect relationship for radiation induced cancer is tested by use of natural radiation making use of selectivity on type of cancer, smoking habits, sex, age group, geographic area and/or time period. For lung cancer, a linear interpolation between zero dose-zero effect and the data from radon-induced cancers in miners implies that the majority of all lung cancers among non-smokers are due to radon; since lung cancers in miners are mostly small-cell undifferentiated (SCU), a rather rare type in general, linearity over predicts the frequency of SCU lung cancers among non smokers by a factor of 10, and among non-smoking females age 25-44 by a factor of 24. Similarly, linearity predicts that the majority of all lung cancers early in this century were due to radon even after due consideration is given to cases missed by poor diagnostic efficiency (this matter is considered in some detail). For the 30-40 age range, linearity over predicts the total lung cancer rate at that time by a factor of 3-6; for SCU lung cancer, the over-prediction is by at least a factor of 10. Other causes of lung cancer are considered which further enhance the degree to which the linearity assumption over-estimates the effects of low level radiation. A similar analysis is applied to leukemia induced by natural radiation. It is concluded that the upper limit for this is not higher than estimates from the linearity hypothesis. (author)

Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

International Nuclear Information System (INIS)

Jeong, Shin Young; Lee, Jaetae

2010-01-01

Radioactive iodine ( 131 I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, 131 I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the 131 I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of 131 I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, candidiasis, and neoplasia. Prevention of 131 I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently interventional sialoendoscopy has been introduced an effective tool for the management of patients with 131 I-induced sialadenitis that is unresponsive to medical treatment.

Adaptive response of spermatogenic cell apoptosis selectively induced by low dose X-ray irradiation in mice

International Nuclear Information System (INIS)

Liu Guangwei; Dong Lihua; Liu Yang; Lv Zhe; Liu Shuchun; Gong Shouliang

2003-01-01

Objective: The adaptive response of spermatogenic cell apoptosis induced by whole-body X-ray irradiation at low doses was studied in mice. Methods: Kunming male mice were irradiated with an inductive dose (D1:75 mGy) and/or a challenging dose (D2:1.0, 2.0 or 3.0 Gy). Different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptotic percentages were analysed using flow cytometry (FCM). Results: When the mice were irradiated with D1 6 h before irradiation with D2, the apoptotic percentages of the spermatogonia and spermatocytes declined rapidly as compared with those in the groups irradiated with D2 only, and those of spermatids and spermatozoa showed no significant changes. When the interval times between D1 and D2 was 3, 6, 12 or 24 h, the apoptotic percentages in spermatogonia and spermatocytes reduced early, significantly and continued for a longer duration after smaller D2(1.0 and 2.0 Gy) irradiation, while the apoptotic percentages did not change after larger D2(3.0 Gy) irradiation. Conclusion: The adaptive response of apoptosis in spermatogonia and spermatocytes could be selectively induced by low dose X-ray irradiation. The adaptive response could be closely related to the D2 dose and interval time between D1 and D2

Sustained Low-Dose Treatment with the Histone Deacetylase Inhibitor LBH589 Induces Terminal Differentiation of Osteosarcoma Cells

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Jason E. Cain

2013-01-01

Full Text Available Histone deacetylase inhibitors (HDACi were identified nearly four decades ago based on their ability to induce cellular differentiation. However, the clinical development of these compounds as cancer therapies has focused on their capacity to induce apoptosis in hematologic and lymphoid malignancies, often in combination with conventional cytotoxic agents. In many cases, HDACi doses necessary to induce these effects result in significant toxicity. Since osteosarcoma cells express markers of terminal osteoblast differentiation in response to DNA methyltransferase inhibitors, we reasoned that the epigenetic reprogramming capacity of HDACi might be exploited for therapeutic benefit. Here, we show that continuous exposure of osteosarcoma cells to low concentrations of HDACi LBH589 (Panobinostat over a three-week period induces terminal osteoblast differentiation and irreversible senescence without inducing cell death. Remarkably, transcriptional profiling revealed that HDACi therapy initiated gene signatures characteristic of chondrocyte and adipocyte lineages in addition to marked upregulation of mature osteoblast markers. In a mouse xenograft model, continuous low dose treatment with LBH589 induced a sustained cytostatic response accompanied by induction of mature osteoblast gene expression. These data suggest that the remarkable capacity of osteosarcoma cells to differentiate in response to HDACi therapy could be exploited for therapeutic benefit without inducing systemic toxicity.

Lansoprazole induces sensitivity to suboptimal doses of paclitaxel in human melanoma.

Science.gov (United States)

Azzarito, Tommaso; Venturi, Giulietta; Cesolini, Albino; Fais, Stefano

2015-01-28

Tumor acidity is now considered an important determinant of drug-resistance and tumor progression, and anti-acidic approaches, such as Proton Pump inhibitors (PPIs), have demonstrated promising antitumor and chemo-sensitizing efficacy. The main purpose of the present study was to evaluate the possible PPI-induced sensitization of human melanoma cells to Paclitaxel (PTX). Our results show that PTX and the PPI Lansoprazole (LAN) combination was extremely efficient against metastatic melanoma cells, as compared to the single treatments, both in vitro and in vivo. We also showed that acidity plays an important role on the anti-tumor activity of these drugs, being detrimental for PTX activity, while crucial for the synergistic effect of PTX following pretreatment with LAN, due to its nature of pro-drug needing protonation for a full activation. We obtained straightforward results in a human melanoma xenograft model combining well tolerated LAN doses with suboptimal and poorly toxic doses of PTX. With this study we provide a clear evidence that the PPI LAN may be included in new combined therapy of human melanoma together with low doses of PTX. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Possible radioprotective effect of folic acid supplementation on low dose ionizing radiation-induced genomic instability in vitro.

Science.gov (United States)

Padula, Gisel; Ponzinibbio, María Virginia; Seoane, Analia I

2016-08-01

Ionizing radiation (IR) induces DNA damage through production of single and double-strand breaks and reactive oxygen species (ROS). Folic acid (FA) prevents radiation-induced DNA damage by modification of DNA synthesis and/or repair and as a radical scavenger. We hypothesized that in vitro supplementation with FA will decrease the sensitivity of cells to genetic damage induced by low dose of ionizing radiation. Annexin V, comet and micronucleus assays were performed in cultured CHO cells. After 7 days of pre-treatment with 0, 100, 200 or 300 nM FA, cultures were exposed to radiation (100 mSv). Two un-irradiated controls were executed (0 and 100 nM FA). Data were statistically analyzed with X2-test and linear regression analysis (P 0.05). We observed a significantly decreased frequency of apoptotic cells with the increasing FA concentration (P <0.05). The same trend was observed when analyzing DNA damage and chromosomal instability (P <0.05 for 300 nM). Only micronuclei frequencies showed significant differences for linear regression analysis (R2=94.04; P <0.01). Our results have demonstrated the radioprotective effect of folic acid supplementation on low dose ionizing radiation-induced genomic instability in vitro; folate status should be taken into account when studying the effect of low dose radiation in environmental or occupational exposure.

Low-Dose Radiation-Induced Adaptive Response in Polychromatic Mice Erythrocyte as Measured by Acridine Orange Stained Micronuleus Assay

International Nuclear Information System (INIS)

Hee-Sun, K.; Kwang-Hee, Y.; Cha-Soom, K.; Jung-Mi, C.; Gu-Choul, S.; Suk-Young, P.; Kyoung-H, C.; Chong-Soom, K.; Young-Khi, L.; Jae-Ho, W.

2004-01-01

The effect of conditioning pretreatment with 0.01Gy of gamma rays on micronucleated polychromatic erythrocyte (MN-PCE) induction by 2Gy of g-rays was determined in peripheral blood of C3H/He mice. The timing of their administration of challenge doses was 6hr. The response was determined by scoring of Acridine orange dye stained MN-PCEs. The results indicate that low dose gamma ray pretreatment does protect against MN-PCE induction by the challenge g-ray dose. Introduction: An adaptive response induced by low doses of ionizing radiation in vivo reported. Some research team reports that a reduction on MN-PCE of mice caused by the pretreatment was observed [1- 4]. However, there was variability in the amount of the response depending on the time and adaptive dose [3]. This is important because the variation of MN-PCE frequency with time could lead to differences in the interpretation. In this study, differences in the biological effects within the priming dose ranges are discussed. Materials and Methods: Specific pathogen free 5-week-old C3H/He mice, purchased from Shizuoka Laboratory Center (Japan), were kept in clean and conventional environment. When 6 weeks old, the animal were whole body irradiated using irradiator of IBL-437 (137Cs, 0.8Gy/min). After various time intervals, the two groups were administrated to adaptation dose and challenge dose of 0.01Gy and 2Gy, respectively. For experiments, sham-irradiated, only adaptive and challenge dose irradiated groups were run concurrently. Smears were stained and scored using Acridine orange dye method [2]. Statistically significant differences in MN-PCE frequency were determined by comparing tie individual values at each group with the respective control values (challenge dose irradiated group) by using the paired ttest. Results and Discussions: Induced MN by the challenge dose (2Gy) after the pretreatment with 0.01Gy is low to the one induced by the challenge dose alone. In the present study, this estimation for the

Therapeutic Effect of Low Doses of Acenocoumarol in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats

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Zygmunt Warzecha

2017-04-01

Full Text Available Intravascular activation of coagulation is observed in acute pancreatitis and is related to the severity of this inflammation. The aim of our study was to evaluate the impact of acenocoumarol therapy on the course of acute pancreatitis induced in male rats by pancreatic ischemia followed by reperfusion. Acenocoumarol at a dose of 50, 100, or 150 µg/kg/dose was administered intragastrically once a day, starting the first dose 24 h after the initiation of pancreatic reperfusion. Results: Histological examination showed that treatment with acenocoumarol reduces pancreatic edema, necrosis, and hemorrhages in rats with pancreatitis. Moreover, the administration of acenocoumarol decreased pancreatic inflammatory infiltration and vacuolization of pancreatic acinar cells. These findings were accompanied with a reduction in the serum activity of lipase and amylase, concentration of interleukin-1β, and plasma d-Dimer concentration. Moreover, the administration of acenocoumarol improved pancreatic blood flow and pancreatic DNA synthesis. Acenocoumarol given at a dose of 150 µg/kg/dose was the most effective in the treatment of early phase acute pancreatitis. However later, acenocoumarol given at the highest dose failed to exhibit any therapeutic effect; whereas lower doses of acenocoumarol were still effective in the treatment of acute pancreatitis. Conclusion: Treatment with acenocoumarol accelerates the recovery of ischemia/reperfusion-induced acute pancreatitis in rats.

Radiation-Induced Noncancer Risks in Interventional Cardiology: Optimisation of Procedures and Staff and Patient Dose Reduction

Science.gov (United States)

Khairuddin Md Yusof, Ahmad

2013-01-01

Concerns about ionizing radiation during interventional cardiology have been increased in recent years as a result of rapid growth in interventional procedure volumes and the high radiation doses associated with some procedures. Noncancer radiation risks to cardiologists and medical staff in terms of radiation-induced cataracts and skin injuries for patients appear clear potential consequences of interventional cardiology procedures, while radiation-induced potential risk of developing cardiovascular effects remains less clear. This paper provides an overview of the evidence-based reviews of concerns about noncancer risks of radiation exposure in interventional cardiology. Strategies commonly undertaken to reduce radiation doses to both medical staff and patients during interventional cardiology procedures are discussed; optimisation of interventional cardiology procedures is highlighted. PMID:24027768

Single Low-Dose Ionizing Radiation Induces Genotoxicity in Adult Zebrafish and its Non-Irradiated Progeny.

Science.gov (United States)

Lemos, J; Neuparth, T; Trigo, M; Costa, P; Vieira, D; Cunha, L; Ponte, F; Costa, P S; Metello, L F; Carvalho, A P

2017-02-01

This study investigated to what extent a single exposure to low doses of ionizing radiation can induce genotoxic damage in irradiated adult zebrafish (Danio rerio) and its non-irradiated F1 progeny. Four groups of adult zebrafish were irradiated with a single dose of X-rays at 0 (control), 100, 500 and 1000 mGy, respectively, and couples of each group were allowed to reproduce following irradiation. Blood of parental fish and whole-body offspring were analysed by the comet assay for detection of DNA damage. The level of DNA damage in irradiated parental fish increased in a radiation dose-dependent manner at day 1 post-irradiation, but returned to the control level thereafter. The level of DNA damage in the progeny was directly correlated with the parental irradiation dose. Results highlight the genotoxic risk of a single exposure to low-dose ionizing radiation in irradiated individuals and also in its non-irradiated progeny.

Carbon dioxide inhalation induces dose-dependent and age-related negative affectivity.

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Eric J Griez

Full Text Available BACKGROUND: Carbon dioxide inhalation is known to induce an emotion similar to spontaneous panic in Panic Disorder patients. The affective response to carbon dioxide in healthy subjects was not clearly characterized yet. METHODOLOGY/PRINCIPAL FINDINGS: Sixty-four healthy subjects underwent a double inhalation of four mixtures containing respectively 0, 9, 17.5 and 35% CO(2 in compressed air, following a double blind, cross-over, randomized design. Affective responses were assessed according to DSM IV criteria for panic, using an Electronic Visual Analogue Scale and the Panic Symptom List. It was demonstrated that carbon dioxide challenges induced a dose dependent negative affect (p<0.0001. This affect was semantically identical to the DSM IV definition of panic. Older individuals were subjectively less sensitive to Carbon Dioxide (p<0.05. CONCLUSIONS/SIGNIFICANCE: CO(2 induced affectivity may lay on a continuum with pathological panic attacks. Consistent with earlier suggestions that panic is a false biological alarm, the affective response to CO(2 may be part of a protective system triggered by suffocation and acute metabolic distress.

A Single Sub-anesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

Science.gov (United States)

Wang, Jing; Goffer, Yossef; Xu, Duo; Tukey, David S.; Shamir, D. B.; Eberle, Sarah E.; Zou, Anthony H.; Blanck, Thomas J.J.; Ziff, Edward B.

2011-01-01

Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its anti-nociceptive properties. Methods We examined whether the spared nerve injury (SNI) model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats SNI-induced depression. Results SNI-treated rats, compared with control, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10mg/kg) did not alter SNI-induced hypersensitivity; however, it treated SNI-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain. PMID:21934410

Induced mitotic gynogenesis in common carp (Cyprinus carpio L.), optimizing irradiation dose of X- and gamma-ray

International Nuclear Information System (INIS)

Yousefian, M.; Amirinia, C.; Bercsenyi, M.; Horvath, L.

1997-01-01

Mitotic gynogenesis was induced in common carp, Cyprinus carpio L., in hatchery and laboratory conditions, using 60Co gamma-ray and X-ray for inactivation of sperm DNA and a subsequent heat shock for inducing endomitosis. The parameter examined was the dose of irradiation in the range of 70-140 Krad. Carp spermatozoa irradiated by 70-100 Krad doses showed higher motility and fertilization ability than the ones irradiated by 110-140 Krad. Sperm treated with doses of 70-90 Krad showed the same fertility rate, but lower survival rate at embryo stage compared with 100 Krad. The shock temperature and duration applied in these experiments for restoration of diploidy level were 40 degrees C plus/minus 0.1 and 2 min., respectively. The highest frequency of mitotic gynogenetic larvae was achieved by 100 Krad 60Co gamma ray at 34 min. after fertilization, - up to 12.2 percent (at 23 degrees C incubating temperature)

Correlation between γ-ray-induced DNA double-strand breakage and cell killing after biologically relevant doses: analysis by pulsed-field gel electrophoresis

International Nuclear Information System (INIS)

Murray, D.

1994-01-01

We examined the degree of correlation between γ-ray-induced lethality and DNA double-strand breaks (dsbs) after biologically relevant doses of radiation. Radiation lethality was modified by treating 14 C-labelled Chinese hamster ovary cells with either of two aminothiols (WR-1065 or WR-255591) and the associated effect on dsb induction was determined by pulsed-field gel electrophoresis (PFGE). The use of phosphorimaging to analyse the distribution of 14 C-activity in the gel greatly improved the low-dose resolution of the PFGE assay. Both WR-1065 and WR-255591 protected against dsb induction and lethality to a similar extent after low doses of radiation. although this correlation broke down when supralethal doses were used to induce dsbs. Thus, the level of dsbs induced in these cells as measured by PFGE after survival-curve doses of γ-radiation is consistently predictive of the degree of lethality obtained, implying a cause-effect relationship between these two parameters and confirming previous results obtained using the neutral filter elution assay for dsbs. (author)

Radiation Sialadenitis Induced by High-dose Radioactive Iodine Therapy

Energy Technology Data Exchange (ETDEWEB)

Jeong, Shin Young; Lee, Jaetae [Kyungpook National University Hospital, Daegu (Korea, Republic of)

2010-06-15

Radioactive iodine ({sup 131}I) is accumulated in the thyroid tissue and plays an important role in the treatment of differentiated papillary and follicular cancers after thyroidectomy. Simultaneously, {sup 131}I is concentrated in the salivary glands and secreted into the saliva. Dose-related damage to the salivary parenchyma results from the {sup 131}I irradiation. Salivary gland swelling and pain, usually involving the parotid, can be seen. The symptoms may develop immediately after a therapeutic dose of {sup 131}I and/or months later and progress in intensity with time. In conjunction with the radiation sialadenitis, secondary complications reported include xerostomia, taste alterations, infection, increases in caries, facial nerve involvement, candidiasis, and neoplasia. Prevention of {sup 131}I sialadenitis may involve the use of sialogogic agents to hasten the transit time of the radioactive iodine through the salivary glands. However, studies are not available to delineate the efficacy of this approach. Treatment of the varied complications that may develop encompass numerous approaches and include gland massage, sialogogic agents, duct probing, antibiotics, mouthwashes, good oral hygiene, and adequate hydration. Recently interventional sialoendoscopy has been introduced an effective tool for the management of patients with {sup 131}I-induced sialadenitis that is unresponsive to medical treatment.

Ultraviolet radiation induces dose-dependent pigment dispersion in crustacean chromatophores.

Science.gov (United States)

Gouveia, Glauce Ribeiro; Lopes, Thaís Martins; Neves, Carla Amorim; Nery, Luiz Eduardo Maia; Trindade, Gilma Santos

2004-10-01

Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm(2) for UVA and 2.15 J/cm(2) for UVB. Maximal response was achieved with 10.0 J/cm(2) UVA and 8.6 J/cm(2) UVB. UVA was more effective than UVB in inducing pigment dispersion. Soon after UV exposure, melanophores once again reached the initial stage of pigment aggregation after 45 min. Aggregated erythrophores of shrimps adapted to a white background showed significant pigment dispersion with 2.5 J/cm(2) UVA and 0.29 J/cm(2) UVC. Dispersed erythrophores of shrimps adapted to a black background did not show any significant response to UVA, UVB or UVC radiation. UVB did not induce any significant pigment dispersion in shrimps adapted to either a white or a black background. As opposed to the tanning response, which only protects against future UV exposure, the pigment dispersion response could be an important agent protecting against the harmful effects of UV radiation exposure.

Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points - An international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial

DEFF Research Database (Denmark)

Puhringer, F.K.; Rex, C.; Sielenkamper, A.W.

2008-01-01

Background: Sugammadex (Org 25969), a novel, selective relaxant binding agent, was specifically designed to rapidly reverse rocuronium-induced neuromuscular blockade. The efficacy and safety of sugammadex for the reversal of profound, high-dose rocuronium-induced neuromuscular blockade...... was evaluated. Methods: A total of 176 adult patients were randomly assigned to receive sugammadex (2, 4, 8, 12, or 16 mg/kg) or placebo at 3 or 15 min after high-dose rocuronium (1.0 or 1.2 mg/kg) during propofol anesthesia. The primary endpoint was time to recovery of the train-of-four ratio to 0.......9. Neuromuscular monitoring was performed using acceleromyography. Results: Sugammadex administered 3 or 15 min after injection of 1 mg/kg rocuronium decreased the median recovery time of the train-of-four ratio to 0.9 in a dose-dependent manner from 111.1 min and 91.0 min (placebo) to 1.6 min and 0.9 min (16 mg...

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54-56 Gy given in 9-7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size.

Science.gov (United States)

Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

2015-04-22

Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003-2008, 41 patients with 42 lung tumors were treated with SBRT to 54-56 Gy in 9-7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16-48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10-55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

Resolution of methylphenidate osmotic release oral system-induced hair loss in two siblings after dose escalation.

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Ardic, Ulku Akyol; Ercan, Eyup Sabri

2017-11-01

This report describes the cases of two siblings who experienced hair loss after treatment with methylphenidate (MPH) osmotic release oral system (OROS). Hair loss was resolved after discontinuation of the drug, but the children re-initiated treatment, after which hair loss again occurred, but they continued the treatment. After dose escalation, the hair loss resolved. This is the first report to describe resolution of OROS-MPH-induced hair loss after dose escalation. © 2017 Japan Pediatric Society.

MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor.

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Tran, Hai-Quyen; Chung, Yoon Hee; Shin, Eun-Joo; Tran, The-Vinh; Jeong, Ji Hoon; Jang, Choon-Gon; Nah, Seung-Yeol; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung-Chun

2017-11-01

Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N-methyl-d-aspartate (NMDA) receptor subunits (GluN1induced ultrastructural degeneration in the hippocampus. A non-competitive NMDA receptor antagonist, MK-801, attenuated these effects of high-dose DM, whereas an opioid antagonist, naloxone, did not affect DM-induced neurotoxicity. Moreover, pretreatment with a highly specific GluN2B subunit inhibitor, traxoprodil, was selectively effective in preventing DM-induced c-Fos expression and apoptotic changes. These results suggest that high-dose DM produces convulsive behaviors by activating GluN2B/NMDA signaling that leads to pro-apoptotic changes. Copyright © 2017. Published by Elsevier Inc.

Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

Science.gov (United States)

Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

2012-09-01

UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

c-Jun/AP-1 pathway-mediated cyclin D1 expression participates in low dose arsenite-induced transformation in mouse epidermal JB6 Cl41 cells

International Nuclear Information System (INIS)

Zhang Dongyun; Li Jingxia; Gao Jimin; Huang Chuanshu

2009-01-01

Arsenic is a well-documented human carcinogen associated with skin carcinogenesis. Our previous work reveals that arsenite exposure is able to induce cell transformation in mouse epidermal cell JB6 Cl41 through the activation of ERK, rather than JNK pathway. Our current studies further evaluate downstream pathway in low dose arsenite-induced cell transformation in JB6 Cl41 cells. Our results showed that treatment of cells with low dose arsenite induced activation of c-Jun/AP-1 pathway, and ectopic expression of dominant negative mutant of c-Jun (TAM67) blocked arsenite-induced transformation. Furthermore, our data indicated that cyclin D1 was an important downstream molecule involved in c-Jun/AP-1-mediated cell transformation upon low dose arsenite exposure, because inhibition of cyclin D1 expression by its specific siRNA in the JB6 Cl41 cells resulted in impairment of anchorage-independent growth of cells induced by low dose arsenite. Collectively, our results demonstrate that c-Jun/AP-1-mediated cyclin D1 expression is at least one of the key events implicated in cell transformation upon low dose arsenite exposure

Evaluation of induced activity, decay heat and dose rate distribution after shutdown in ITER

Energy Technology Data Exchange (ETDEWEB)

Maki, Koichi [Hitachi Ltd., Ibaraki (Japan). Hitachi Research Lab.; Satoh, Satoshi; Hayashi, Katsumi; Yamada, Koubun; Takatsu, Hideyuki; Iida, Hiromasa

1997-03-01

Induced activity, decay heat and dose rate distributions after shutdown were estimated for 1MWa/m{sup 2} operation in ITER. The activity in the inboard blanket one day after shutdown is 1.5x10{sup 11}Bq/cm{sup 3}, and the average decay heating rate 0.01w/cm{sup 3}. The dose rate outside the 120cm thick concrete biological shield is two order higher than the design criterion of 5{mu}Sv/h. This indicates that the biological shield thickness should be enhanced by 50cm in concrete, that is, total thickness 170cm for workers to enter the reactor room and to perform maintenance. (author)

A Voxel-Based Approach to Explore Local Dose Differences Associated With Radiation-Induced Lung Damage

Energy Technology Data Exchange (ETDEWEB)

Palma, Giuseppe [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Monti, Serena [IRCCS SDN, Naples (Italy); D' Avino, Vittoria [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Conson, Manuel [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Liuzzi, Raffaele [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Pressello, Maria Cristina [Department of Health Physics, S. Camillo-Forlanini Hospital, Rome (Italy); Donato, Vittorio [Department of Radiation Oncology, S. Camillo-Forlanini Hospital, Rome (Italy); Deasy, Joseph O. [Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, NY (United States); Quarantelli, Mario [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Pacelli, Roberto [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy); Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples (Italy); Cella, Laura, E-mail: laura.cella@cnr.it [Institute of Biostructure and Bioimaging, National Research Council, Naples (Italy)

2016-09-01

Purpose: To apply a voxel-based (VB) approach aimed at exploring local dose differences associated with late radiation-induced lung damage (RILD). Methods and Materials: An interinstitutional database of 98 patients who were Hodgkin lymphoma (HL) survivors treated with postchemotherapy supradiaphragmatic radiation therapy was analyzed in the study. Eighteen patients experienced late RILD, classified according to the Radiation Therapy Oncology Group scoring system. Each patient's computed tomographic (CT) scan was normalized to a single reference case anatomy (common coordinate system, CCS) through a log-diffeomorphic approach. The obtained deformation fields were used to map the dose of each patient into the CCS. The coregistration robustness and the dose mapping accuracy were evaluated by geometric and dose scores. Two different statistical mapping schemes for nonparametric multiple permutation inference on dose maps were applied, and the corresponding P<.05 significance lung subregions were generated. A receiver operating characteristic (ROC)-based test was performed on the mean dose extracted from each subregion. Results: The coregistration process resulted in a geometrically robust and accurate dose warping. A significantly higher dose was consistently delivered to RILD patients in voxel clusters near the peripheral medial-basal portion of the lungs. The area under the ROC curves (AUC) from the mean dose of the voxel clusters was higher than the corresponding AUC derived from the total lung mean dose. Conclusions: We implemented a framework including a robust registration process and a VB approach accounting for the multiple comparison problem in dose-response modeling, and applied it to a cohort of HL survivors to explore a local dose–RILD relationship in the lungs. Patients with RILD received a significantly greater dose in parenchymal regions where low doses (∼6 Gy) were delivered. Interestingly, the relation between differences in the high-dose

Bisphenol A (BPA) aggravates multiple low-dose streptozotocin-induced Type 1 diabetes in C57BL/6 mice.

Science.gov (United States)

Cetkovic-Cvrlje, Marina; Thinamany, Sinduja; Bruner, Kylie A

2017-12-01

Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disorder characterized by destruction of insulin-producing pancreatic β-cells. Whereas epidemiological data implicate environmental factors in the increasing incidence of T1D, their identity remains unknown. Though exposure to bisphenol A (BPA) has been associated with several disorders, no epidemiologic evidence has linked BPA exposure and T1D. The goal of this study was to elucidate diabetogenic potentials of BPA and underlying mechanisms in the context of T-cell immunity, in a multiple low-dose streptozotocin (MLDSTZ)-induced autoimmune mouse T1D model. C57BL/6 mice were orally exposed to 1 or 10 mg BPA/L starting at 4 wk of age; diabetes was induced at 9 wk of age with STZ. T-cell composition, function, and insulitis levels were studied at Days 11 and 50 during diabetes development (i.e. post-first STZ injection). Results showed both BPA doses increased diabetes incidence and affected T-cell immunity. However, mechanisms of diabetogenic action appeared divergent based on dose. Low-dose BPA fits a profile of an agent that exhibits pro-diabetogenic effects via T-cell immunomodulation in the early stages of disease development, i.e. decreases in splenic T-cell subpopulations [especially CD4 + T-cells] along with a trend in elevation of splenic T-cell formation of pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6). In contrast, high-dose BPA did not affect T-cell populations and led to decreased levels of IFN-γ and TNF-α. Both treatments did not affect insulitis levels at the disease early stage, but aggravated it later on. By the study end, besides decreasing T-cell proliferative capacity, low-dose BPA did not affect other T-cell-related parameters, including cytokine secretion, comparable to the effects of high-dose BPA. In conclusion, this study confirmed BPA as a potential diabetogenic compound with immunomodulatory mechanisms of action - in the context of T-cell immunity - that seemed to be dose

Adaptive response induced by low doses of ionizing radiation in human lymphocytes

International Nuclear Information System (INIS)

Frati, Diego Libkind; Bunge, Maria M.

2001-01-01

The term adaptive response (AR) applies to the phenomenon of protection or enhanced repair induced by a small dose of a mutagenic agent. In order to determine the existence of AR in human lymphocytes for two different irradiation schemes, microcultures of blood from 4 donors were irradiated. Samples were exposed 24 hours (hr) after phytohemagglutinin stimulation to an adapting dose of 0,01 Gy and to a challenging dose of 1,5 Gy either 6 or 24 hr later (irradiation scheme 24+30 or 24+48, respectively). Gamma radiation from a 2,5 MeV Linac was used in all experiments. A cytogenetic analysis of unstable chromosome aberrations was applied as the endpoint. High inter-individual variability was found for the first irradiation scheme: one expressed AR, two did not and the last showed an apparent synergistic response. For the second irradiation scheme, low mitotic indices (MI) were found, suggesting a G2 arrest. When a series of harvesting times were applied for the last donor, normal MI were obtained only harvesting after 58 hr. An AR was found when harvesting at 72 hr but not at 58 hr. (author)

New model for assessing dose and dose rate sensitivity of Gamma ray radiation loss in polarization maintaining optical fibers

International Nuclear Information System (INIS)

Zhang Hongchen; Liu Hai; Qiao Wenqiang; Xue Huijie; He Shiyu

2012-01-01

Highlights: ► Building a new phenomenological theory model to investigate the relation about the irradiation induced loss with irradiation dose and dose rate. ► The Gamma ray irradiation induced loss of the “Capsule” type and “Panda” type polarization maintaining optical fibers at 1310 nm wavelength are investigated. ► The anti irradiation performance of the “Panda” type polarization maintaining optical fiber is better than that of the “Capsule” type polarization maintaining optical fiber, the reason is that the stress region doped by GeO 2 . - Abstract: The Gamma ray irradiation induced loss of the “Capsule” type and “Panda” type polarization maintaining optical fibers at 1310 nm wavelength are investigated. A phenomenological theory model is introduced and the influence of irradiation dose and dose rate on the irradiation induced loss is discussed. The phenomenological theoretical results are consistent with the experimental results of the irradiation induced loss for the two types of polarization maintaining optical fibers. The anti irradiation performance of the “Panda” type polarization maintaining optical fiber is better than that of the “Capsule” type polarization maintaining optical fiber, the reason is that the stress region dope with GeO 2 . Meanwhile, both of the polarization maintaining optical fiber irradiation induced loss increase with increasing the irradiation dose. In the case of same dose, the high dose rate Gamma ray irradiation induced optical fiber losses are higher than that of the low dose rate.

Taenia crassiceps Infection Attenuates Multiple Low-Dose Streptozotocin-Induced Diabetes

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Arlett Espinoza-Jiménez

2010-01-01

Full Text Available Taenia crassiceps, like other helminths, can exert regulatory effects on the immune system of its host. This study investigates the effect of chronic T. crassiceps infection on the outcome of Multiple Low Dose Streptozotocin-Induced Diabetes (MLDS. Healthy or previously T. crassiceps-infected mice received MLDS and type 1 diabetes (T1D symptoms were evaluated for 6 weeks following the induction of MLDS. T. crassiceps-infected mice displayed lower blood glucose levels throughout the study. A significantly lower percentage of T. crassiceps-infected mice (40% developed T1D compared to the uninfected group (100%. Insulitis was remarkably absent in T. crassiceps-infected mice, which had normal pancreatic insulin content, whereas uninfected mice showed a dramatic reduction in pancreatic insulin. Infected mice that received MLDS did not show an increase in their regulatory T cell population, however, they had a greater number of alternatively activated macrophages, higher levels of the cytokine IL-4, and lower levels of TNF-α. Therefore, infection with T. crassiceps causes an immunomodulation that modifies the incidence and development of MLDS-induced autoimmune diabetes.

Human lymphocytes exposed to low doses of ionizing radiations become refractory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA

International Nuclear Information System (INIS)

Wolff, Sheldon; Afzal, Veena; Wiencke, J.K.; Olivieri, G.; Michaeli, A.

1988-01-01

The results indicate that prior exposure to 0.01 Gy of X-rays reduces the number of chromosome breaks induced by double-strand breaks, and perhaps even by cross-links, in DNA, but has the opposite effect on breaks induced by the alkylating agent MMS. The results also show that the induced repair mechanism is different from that observed in the adaptive reponse that follows exposure to low doses of alkylating agents. (author)

Bimodal cell death induced by high radiation doses in the radioresistant sf9 insect cell line

International Nuclear Information System (INIS)

Chandna, S.

2003-01-01

Full text: This study was conducted to investigate the mode(s) of cell death induced by high radiation doses in the highly radioresistant Sf9 insect ovarian cell line. Methods: Cells were exposed to γ-radiation doses 200Gy and 500Gy, harvested at various time intervals (6h-72h) following irradiation, and subjected to cell morphology assay, DNA agarose gel electrophoresis, single cell gel electrophoresis (SCGE; comet assay) and Annexin-V labeling for the detection of membrane phosphatidylserine externalization. Cell morphology was assessed in cells entrapped and fixed in agarose gel directly from the cell suspension, thus preventing the possible loss of fragments/ apoptotic bodies. Surviving fraction of Sf9 cells was 0.01 at 200Gy and 98%) undergoing extensive DNA fragmentation at 500Gy, whereas the frequency of cells with DNA fragmentation was considerably less (∼12%) at 200Gy. Conclusions: While the mode of cell death at 200Gy seems to be different from typical apoptosis, a dose of 500Gy induced bimodal cell death, with typical apoptotic as well as the atypical cell death observed at 200Gy

Time-effect relationship of immunological adaptive response induced by low dose X-irradiation in mice

International Nuclear Information System (INIS)

Zhao Yong; Gong Shouliang; Liu Shuzheng

1995-01-01

Kunming mice irradiated with whole-body X-rays were used to observe time-effect relationship of immunological adaptive response induced by ionizing radiation. The results showed that pre-irradiation dose of 75 mGy X-rays with the intervals of 6-48 h between pre-irradiation and challenge irradiation could induce immunological adaptive response in the spontaneous proliferation of thymocytes and the responses of splenocytes to Con A and LPS in mice at 18-24 h after challenge irradiation with 1.5-2.0 Gy X-rays

Plutonium dose-effect relationship

International Nuclear Information System (INIS)

Matsuoka, Osamu

1976-01-01

Dose in internal exposure to Pu was investigated, and dose-effect relationship was discussed. Dose-effect relationship in internal exposure was investigated by means of two methods, which were relationship between dose and its effect (relationship between μ Ci/Kg and its effect), and exposure dose and its effects (rad-effect), and merits and demerits of two methods were mentioned. Problems in a indication method such as mean dose were discussed with respect to the dose in skeleton, the liver and the lung. Pu-induced osteosarcoma in mice rats, and beagles was described, and differences in its induction between animals were discussed. Pulmonary neoplasma induced by 239 PuO 2 inhalation in beagles was reported, and description was made as to differences in induction of lung cancer between animals when Pu was inhaled and was taken into the lung. A theoretical and experimental study of a extrapolation of the results of the animal experiment using Pu to human cases is necessary. (Serizawa, K.)

Retrospective Cohort Study of Bronchial Doses and Radiation-Induced Atelectasis After Stereotactic Body Radiation Therapy of Lung Tumors Located Close to the Bronchial Tree

International Nuclear Information System (INIS)

Karlsson, Kristin; Nyman, Jan; Baumann, Pia; Wersäll, Peter; Drugge, Ninni; Gagliardi, Giovanna; Johansson, Karl-Axel; Persson, Jan-Olov; Rutkowska, Eva; Tullgren, Owe; Lax, Ingmar

2013-01-01

Purpose: To evaluate the dose–response relationship between radiation-induced atelectasis after stereotactic body radiation therapy (SBRT) and bronchial dose. Methods and Materials: Seventy-four patients treated with SBRT for tumors close to main, lobar, or segmental bronchi were selected. The association between incidence of atelectasis and bronchial dose parameters (maximum point-dose and minimum dose to the high-dose bronchial volume [ranging from 0.1 cm 3 up to 2.0 cm 3 ]) was statistically evaluated with survival analysis models. Results: Prescribed doses varied between 4 and 20 Gy per fraction in 2-5 fractions. Eighteen patients (24.3%) developed atelectasis considered to be radiation-induced. Statistical analysis showed a significant correlation between the incidence of radiation-induced atelectasis and minimum dose to the high-dose bronchial volumes, of which 0.1 cm 3 (D 0.1cm3 ) was used for further analysis. The median value of D 0.1cm3 (α/β = 3 Gy) was EQD 2,LQ = 147 Gy 3 (range, 20-293 Gy 3 ). For patients who developed atelectasis the median value was EQD 2,LQ = 210 Gy 3 , and for patients who did not develop atelectasis, EQD 2,LQ = 105 Gy 3 . Median time from treatment to development of atelectasis was 8.0 months (range, 1.1-30.1 months). Conclusion: In this retrospective study a significant dose–response relationship between the incidence of atelectasis and the dose to the high-dose volume of the bronchi is shown

Hand-foot syndrome in a patient with metastatic lung adenocarcinoma induced by high-dose icotinib: A case report and review of the literature.

Science.gov (United States)

Zheng, Yulong; Fang, Weijia; Xu, Nong

2012-12-01

Icotinib is a new oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). The most frequent side-effects of icotinib include rash and diarrhea. Hand-foot syndrome (HFS) induced by EGFR-TKI is rare. The present study describes, for the first time, HFS induced by high-dose icotinib in a 65-year old female with metastatic lung adenocarcinoma. The patient developed HFS during the first week of icotinib treatment with characteristic clinical presentation. HFS regressed after icotinib dose-reduction was initiated. HFS may occur with icotinib, especially when administered in high doses.

In vitro and in vivo effects of low dose HTO contamination modulated by dose rate

International Nuclear Information System (INIS)

Petcu, I.; Savu, D.; Moisoi, N.; Koeteles, G.J.

1997-01-01

The experiment performed in vitro intended to examine whether an adaptive response could be elicited on lymphocytes by low-level contamination of whole blood with tritiated water and if the modification of the dose rate has any influence on it. Lymphocytes pre-exposed to 3 HOH (0.2 - 6.6 MBq/ml) and subsequently irradiated with I Gy γ-rays showed micronuclei frequency significantly lower (40% - 45%) than the expected member (sum of the yields induced by 3 HOH and γ-rays separately). The degree of the radioresistance induced by HTO pre-treatments became higher with decreasing dose-rate for a rather similar total adapting dose. In vivo, the aim of the study was to investigate if different dose rates are inducing modulation of the lipid peroxidation level and of the thymidine uptake in different tissues of animals contaminated by HTO ingestion. The total doses varied between 5 and 20 cGy and were delivered as chronic (100 days) or acute contamination (5 days). It was observed that only doses about 20 cGy caused a dose-rate dependent increase of the lipid peroxidation level in the tissues of small intestine, kidney and spleen. Both chronic and acute contamination did produce reduced incorporation of thymidine in the cells of bone marrow. The most effective decrease of thymidine uptake was induced by the acute contamination in the lower dose domain (approx. 5 cGy). Our hypothesis is that in this dose domain the modification of thymidine uptake could be due to changes at the level of membrane transport. (author)

In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

Energy Technology Data Exchange (ETDEWEB)

Langer, R.D., E-mail: rlanger@uaeu.ac.ae [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Lorke, D.E. [Florida International University, Miami, FL (United States); Neidl van Gorkom, K.F. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Petroianu, G. [Florida International University, Miami, FL (United States); Azimullah, S.; Nurulain, S.M.; Singh, S. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Fuchsjäger, M. [Al Ain Hospital, MUV-VAMED, Al Ain (United Arab Emirates)

2012-10-15

Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA.

In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

International Nuclear Information System (INIS)

Langer, R.D.; Lorke, D.E.; Neidl van Gorkom, K.F.; Petroianu, G.; Azimullah, S.; Nurulain, S.M.; Singh, S.; Fuchsjäger, M.

2012-01-01

Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA

Clustered DNA damages induced in isolated DNA and in human cells by low doses of ionizing radiation

Science.gov (United States)

Sutherland, B. M.; Bennett, P. V.; Sidorkina, O.; Laval, J.; Lowenstein, D. I. (Principal Investigator)

2000-01-01

Clustered DNA damages-two or more closely spaced damages (strand breaks, abasic sites, or oxidized bases) on opposing strands-are suspects as critical lesions producing lethal and mutagenic effects of ionizing radiation. However, as a result of the lack of methods for measuring damage clusters induced by ionizing radiation in genomic DNA, neither the frequencies of their production by physiological doses of radiation, nor their repairability, nor their biological effects are known. On the basis of methods that we developed for quantitating damages in large DNAs, we have devised and validated a way of measuring ionizing radiation-induced clustered lesions in genomic DNA, including DNA from human cells. DNA is treated with an endonuclease that induces a single-strand cleavage at an oxidized base or abasic site. If there are two closely spaced damages on opposing strands, such cleavage will reduce the size of the DNA on a nondenaturing gel. We show that ionizing radiation does induce clustered DNA damages containing abasic sites, oxidized purines, or oxidized pyrimidines. Further, the frequency of each of these cluster classes is comparable to that of frank double-strand breaks; among all complex damages induced by ionizing radiation, double-strand breaks are only about 20%, with other clustered damage constituting some 80%. We also show that even low doses (0.1-1 Gy) of high linear energy transfer ionizing radiation induce clustered damages in human cells.

Dose-dependent and gender-related radiation-induced transcription alterations of Gadd45a and Ier5 in human lymphocytes exposed to gamma ray emitted by 60Co

International Nuclear Information System (INIS)

Tavakoli, H.; Manoochehri, M.; Mosalla, S. M. M.; Ghafori, M.; Karimi, A. A.

2013-01-01

Growth arrest DNA damage-inducible 45a gene (Gadd45a) and immediate early response gene 5 (Ier5) have been emphasised as ideal radiation bio-markers in several reports. However, some aspects of radiation-induced transcriptional alterations of these genes are unknown. In this study, gender-dependency and dose-dependency as two factors that may affect radiation induced transcription of Gadd45a and Ier5 genes were investigated. Human lymphocyte cells from six healthy voluntary blood donors (three women and three men) were irradiated in vitro with doses of 0.5-4.0 Gy from a 60 Co source and RNA isolated 4 h later using the High Pure RNA Isolation Kit. Dose and gender dependency of radiation-induced transcriptional alterations of Gadd45a and Ier5 genes were studied by quantitative real-time polymerase chain reaction. The results showed that as a whole, Gadd45a and Ier5 gave responses to gamma rays, while the responses were independent of radiation doses. Therefore, regardless of radiation dose, Gadd45a and Ier5 can be considered potential radiation bio-markers. Besides, although radiation-induced transcriptional alterations of Gadd45a in female and male lymphocyte samples were insignificant at 0.5 Gy, at other doses, their quantities in female samples were at a significantly higher level than in male samples. Radiation induced transcription of Ier5 of females samples had a reduction in comparison with male samples at 1 and 2 Gy, but at doses of 0.5 and 4 Gy, females were significantly more susceptible to radiation-induced transcriptional alteration of Ier5. (authors)

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells.

Science.gov (United States)

Kim, J H; Hyun, S J; Yoon, M Y; Ji, Y H; Cho, C K; Yoo, S Y

1997-06-01

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of gamma-rays (0.01 Gy) 4 or 20 hrs prior to high dose gamma-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose gamma-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-beta-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose gamma-ray irradiation to high dose gamma-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.

Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level.

Science.gov (United States)

Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

2015-12-01

The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h(-1) up to 1.5 Gy h(-1). Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h(-1). A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR10) was estimated at 95 ± 7 mGy h(-1), followed by 153 ± 13 mGy h(-1) and 169 ± 12 mGy h(-1) on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h(-1), antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h(-1) which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic stress conditions

Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54–56 Gy given in 9–7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size

International Nuclear Information System (INIS)

Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

2015-01-01

Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003–2008, 41 patients with 42 lung tumors were treated with SBRT to 54–56 Gy in 9–7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16–48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10–55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures

Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer.

Science.gov (United States)

Park, Gab-Jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

2017-01-01

A microdose drug-drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2-9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (C max ) and area under the curve to the last measurement (AUC t ) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for C max , and 4.07 (micro), 4.33 (regular) for AUC t . For the induction study, they were 0.26 (micro) and 0.21 (regular) for C max , and 0.16 (micro) and 0.15 (regular) for AUC t . There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes.

Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees

International Nuclear Information System (INIS)

Shata, Mohamed Tarek; Tricoche, Nancy; Perkus, Marion; Tom, Darley; Brotman, Betsy; McCormack, Patricia; Pfahler, Wolfram; Lee, Dong-Hun; Tobler, Leslie H.; Busch, Michael; Prince, Alfred M.

2003-01-01

In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion

Characterizing dose response relationships: Chronic gamma radiation in Lemna minor induces oxidative stress and altered polyploidy level

International Nuclear Information System (INIS)

Van Hoeck, Arne; Horemans, Nele; Van Hees, May; Nauts, Robin; Knapen, Dries; Vandenhove, Hildegarde; Blust, Ronny

2015-01-01

The biological effects and interactions of different radiation types in plants are still far from understood. Among different radiation types, external gamma radiation treatments have been mostly studied to assess the biological impact of radiation toxicity in organisms. Upon exposure of plants to gamma radiation, ionisation events can cause, either directly or indirectly, severe biological damage to DNA and other biomolecules. However, the biological responses and oxidative stress related mechanisms under chronic radiation conditions are poorly understood in plant systems. In the following study, it was questioned if the Lemna minor growth inhibition test is a suitable approach to also assess the radiotoxicity of this freshwater plant. Therefore, L. minor plants were continuously exposed for seven days to 12 different dose rate levels covering almost six orders of magnitude starting from 80 μGy h"−"1 up to 1.5 Gy h"−"1. Subsequently, growth, antioxidative defence system and genomic responses of L. minor plants were evaluated. Although L. minor plants could survive the exposure treatment at environmental relevant exposure conditions, higher dose rate levels induced dose dependent growth inhibitions starting from approximately 27 mGy h"−"1. A ten-percentage growth inhibition of frond area Effective Dose Rate (EDR_1_0) was estimated at 95 ± 7 mGy h"−"1, followed by 153 ± 13 mGy h"−"1 and 169 ± 12 mGy h"−"1 on fresh weight and frond number, respectively. Up to a dose rate of approximately 5 mGy h"−"1, antioxidative enzymes and metabolites remained unaffected in plants. A significant change in catalase enzyme activity was found at 27 mGy h"−"1 which was accompanied with significant increases of other antioxidative enzyme activities and shifts in ascorbate and glutathione content at higher dose rate levels, indicating an increase in oxidative stress in plants. Recent plant research hypothesized that environmental genotoxic

Evaluation of therapeutic effect of low dose naltrexone in experimentally-induced Crohn's disease in rats.

Science.gov (United States)

Tawfik, Dina Ibrahim; Osman, Afaf Sayed; Tolba, Hedayat Mahmoud; Khattab, Aida; Abdel-Salam, Lubna O; Kamel, Mahmoud M

2016-10-01

Crohn's disease is a relapsing inflammatory condition afflicting the digestive tract. Drugs used for treatment of Crohn's disease may be associated with serious side effects. Endogenous opioid peptides modulate inflammatory cytokine production. Opioid antagonists have been shown to play a role in healing and repair of tissues. This work was designed to detect the possible beneficial effects of opioid antagonist naltrexone in indomethacin-induced Crohn's disease in rats. Enteritis was induced in male albino rats by two subcutaneous injection of indomethacin in a dose of 7.5mg/kg 24h apart started on day one. Salfasalazine, naltrexone and their combination were administered orally from day one of induction of enteritis to day 10. Disease activity index, serum levels of C-reactive protein and tumor necrosis factor-α, macroscopic and microscopic pathological scores and in vitro motility studies were evaluated. Induction of enteritis resulted in significant increase of disease activity index, significant elevation of serum levels of C-reactive protein and tumor necrosis factor-α, significant deterioration of pathological scores and significant increase in the mean contractility response of the isolated ileal segments compared with normal untreated rats. Treatment with sulfasalazine, low dose of natrexone or their combination resulted in significant improvement of all measured parameters compared with enteritis group. The current finding could provide new interesting opportunity for developing new therapeutic approaches for treatment of Crohn's disease. Use of naltrexone, especially in small dose, has little side effects making it of interest for treatment of Crohn's disease. Also, it provides the possibility of reduced doses of other drugs if it is used as combined therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Dose and effect relationship of radiation induced cancer and its influencing factors in experimental animals, 1

International Nuclear Information System (INIS)

Sasaki, Shunsaku; Sato, Fumiaki; Eto, Hideo

1975-01-01

The data of risk evaluation of external irradiation were integrated with animal experiments from the aspects of qualitative generalizations of characteristics of radiation induced tumors. Studies covered competition of cause of death, figure of dose-to-effect relationship, characteristics of low dose rate of irradiation, relative biological effectiveness (RBE) of high LET radiation, effects of feactionated irradiation, complex actions with chemical substances, effects of protectional medium, differences of radiosensitivity by species and strains, and age dependency of sensitivities. Competition of cause of death by time length of latent period and degree of malignancy of the disease. Discussion on competition of death suggested the following idea: 1) incidence of tumor induction in the individual level did not correspond to transformation in the cellular level, and 2) relative incidence of tumor induction after a certain dose of whole body irradiation did not indicate the relative sensitivity of each tissue, for the relationship between tumor incidence and exposure dose was not a linear relationship. The dose-to-effect relationship of tumor induction was decided by following factors: i) sensitivity on transformation of cells, ii) sensitivity on the death of potential tumor cells, and iii) competition of the cause of death. Tumor induction by low dose rate irradiation was also studied by comparing qualitative and quantitative differences between high dose rate single irradiation and a series of low dose rate irradiation. (Serizawa, K.)

Caffeine at a Moderate Dose Did Not Affect the Skeletal System of Rats with Streptozotocin-Induced Diabetes

Directory of Open Access Journals (Sweden)

Joanna Folwarczna

2017-10-01

Full Text Available Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally. Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.

Caffeine at a Moderate Dose Did Not Affect the Skeletal System of Rats with Streptozotocin-Induced Diabetes.

Science.gov (United States)

Folwarczna, Joanna; Janas, Aleksandra; Cegieła, Urszula; Pytlik, Maria; Śliwiński, Leszek; Matejczyk, Magdalena; Nowacka, Anna; Rudy, Karolina; Krivošíková, Zora; Štefíková, Kornélia; Gajdoš, Martin

2017-10-30

Diabetes may lead to the development of osteoporosis. Coffee drinking, apart from its health benefits, is taken into consideration as an osteoporosis risk factor. Data from human and animal studies on coffee and caffeine bone effects are inconsistent. The aim of the study was to investigate effects of caffeine at a moderate dose on the skeletal system of rats in two models of experimental diabetes induced by streptozotocin. Effects of caffeine administered orally (20 mg/kg aily for four weeks) were investigated in three-month-old female Wistar rats, which, two weeks before the start of caffeine administration, received streptozotocin (60 mg/kg, intraperitoneally) alone or streptozotocin after nicotinamide (230 mg/kg, intraperitoneally). Bone turnover markers, mass, mineral density, histomorphometric parameters, and mechanical properties were examined. Streptozotocin induced diabetes, with profound changes in the skeletal system due to increased bone resorption and decreased bone formation. Although streptozotocin administered after nicotinamide induced slight increases in glucose levels at the beginning of the experiment only, slight, but significant unfavorable changes in the skeletal system were demonstrated. Administration of caffeine did not affect the investigated skeletal parameters of rats with streptozotocin-induced disorders. In conclusion, caffeine at a moderate dose did not exert a damaging effect on the skeletal system of diabetic rats.

Potential Antioxidant Role of Tridham in Managing Oxidative Stress against Aflatoxin-B1-Induced Experimental Hepatocellular Carcinoma

Directory of Open Access Journals (Sweden)

Vijaya Ravinayagam

2012-01-01

Full Text Available Hepatocellular carcinoma (HCC is one of the most fatal cancers due to delayed diagnosis and lack of effective treatment options. Significant exposure to Aflatoxin B1 (AFB1, a potent hepatotoxic and hepatocarcinogenic mycotoxin, plays a major role in liver carcinogenesis through oxidative tissue damage and p53 mutation. The present study emphasizes the anticarcinogenic effect of Tridham (TD, a polyherbal traditional medicine, on AFB1-induced HCC in male Wistar rats. AFB1-administered HCC-bearing rats (Group II showed increased levels of lipid peroxides (LPOs, thiobarbituric acid substances (TBARs, and protein carbonyls (PCOs and decreased levels of enzymic and nonenzymic antioxidants when compared to control animals (Group I. Administration of TD orally (300 mg/kg body weight/day for 45 days to HCC-bearing animals (Group III significantly reduced the tissue damage accompanied by restoration of the levels of antioxidants. Histological observation confirmed the induction of tumour in Group II animals and complete regression of tumour in Group III animals. This study highlights the potent antioxidant properties of TD which contribute to its therapeutic effect in AFB1-induced HCC in rats.

Neutropenia induced by high-dose intravenous benzylpenicillin in treating neurosyphilis: Does it really matter?

Directory of Open Access Journals (Sweden)

Rui-Rui Peng

2017-03-01

Full Text Available Prompt therapy with high-dose intravenous benzylpenicillin for a prolonged period is critical for neurosyphilis patients to avoid irreversible sequelae. However, life-threatening neutropenia has been reported as a complication of prolonged therapy with high doses of benzylpenicillin when treating other diseases. This study aimed to investigate the incidence, presentation, management and prognosis of benzylpenicillin-induced neutropenia in treating neurosyphilis based on a large sample of syphilis patients in Shanghai.Between 1st January 2013 and 31st December 2015, 1367 patients with neurosyphilis were treated with benzylpenicillin, 578 of whom were eligible for recruitment to this study. Among patients without medical co-morbidities, the total incidence of benzylpenicillin-induced neutropenia and severe neutropenia was 2.42% (95% CI: 1.38-4.13% and 0.35% (95% CI: 0.06-1.39%, respectively. The treatment duration before onset of neutropenia ranged from 10 to 14 days, with a total cumulative dose of between 240 and 324 megaunits of benzylpenicillin. Neutropenia was accompanied by symptoms of chills and fever (5 patients, fatigue (2 patients, cough (1 patient, sore throat (1 patient, diarrhea (1 patient and erythematous rash (1 patient. The severity of neutropenia was not associated with age, gender or type of neurosyphilis (p>0.05. Neutropenia, even when severe, was often tolerated and normalized within one week. A more serious neutropenia did not occur when reinstituting benzylpenicillin in patients with mild or moderate neutropenia nor when ceftriaxone was used three months after patients had previously experienced severe neutropenia.Benzylpenicillin-induced neutropenia was uncommon in our cohort of patients. Continuation of therapy was possible with intensive surveillance for those with mild or moderate neutropenia. For severe neutropenia, it is not essential to aggressively use hematopoietic growth factors or broad-spectrum antibiotics for

Sun-Induced Changes in Stratum Corneum Function Are Gender and Dose Dependent in a Chinese Population

Science.gov (United States)

Liu, Z.; Fluhr, J.W.; Song, S.P.; Sun, Z.; Wang, H.; Shi, Y.J.; Elias, P.M.; Man, M.-Q.

2010-01-01

Previous studies have demonstrated that UVB radiation changes the epidermal permeability barrier and stratum corneum (SC) hydration. It is well known that sun exposure causes erythema, sunburn and melanoma. However, whether daily sun exposure alters SC integrity and epidermal permeability barrier function is largely unknown, especially in Chinese subjects. In the present study, we assess the SC integrity, SC hydration and epidermal permeability barrier function following various doses of sun exposure. A total of 258 subjects (124 males and 134 females) aged 18–50 years were enrolled. A multifunctional skin physiology monitor (Courage & Khazaka MPA5) was used to measure SC hydration and transepidermal water loss (TEWL) on the forearms. In males, basal TEWL was higher with higher doses of sun exposure than with lower doses and control, whereas in females, basal TEWL was higher with lower doses of sun exposure than with higher doses and control. In the group with higher doses of sun exposure, TEWL in females was significantly lower than that in males. The barrier recovery was faster in females than in males in both control and lower-dose groups. In both males and females, barrier recovery was delayed with higher doses of sun exposure. In males, sun exposure did not alter SC hydration, while in females SC hydration was lower with lower doses of sun exposure as compared with control and higher doses of sun exposure. These results demonstrated that sun-induced changes in SC function and SC hydration vary with gender and the extent of sun exposure. PMID:20571289

Chromosomal aberrations induced by low-dose γ-irradiation: Study of R-banded chromosomes of human lymphocytes

International Nuclear Information System (INIS)

Al-Achkar, W.; Lefrancois, D.; Aurias, A.

1991-01-01

The effect of low-dose (0-0.5 Gy) γ-radiations was studied on R-banded chromosomes from lymphocytes of healthy donors of various ages. In cells from newborns, an increase of chromosome damage roughly proportional to the dose was found. In lymphocytes from young adults chromosomal aberrations were not detected at doses of 0.05 and 0.1 Gy, and in lymphocytes from old adults not even at 0.2 Gy. The difficulty in detecting aberrations in lymphocytes from adults is largely due to a considerable background of chromosomal anomalies which should be borne in mind in dosimetry studies. The rate of induction largely depends on the types of rearrangements. One-break terminal deletions are efficiently induced at 0.1 and 0.2 Gy and are the best indicators of exposure at these doses. At 0.5 Gy, the frequencies of 2-break lesions, i.e., dicentrics and reciprocal translocations, increase, whereas the of deletions decreases. (author). 6 refs., 3 figs., 2 tabs

The MARS15-based FermiCORD code system for calculation of the accelerator-induced residual dose

Energy Technology Data Exchange (ETDEWEB)

Grebe, A.; Leveling, A.; Lu, T.; Mokhov, N.; Pronskikh, V.

2018-01-01

The FermiCORD code system, a set of codes based on MARS15 that calculates the accelerator-induced residual doses at experimental facilities of arbitrary configurations, has been developed. FermiCORD is written in C++ as an add-on to Fortran-based MARS15. The FermiCORD algorithm consists of two stages: 1) simulation of residual doses on contact with the surfaces surrounding the studied location and of radionuclide inventories in the structures surrounding those locations using MARS15, and 2) simulation of the emission of the nuclear decay gamma-quanta by the residuals in the activated structures and scoring the prompt doses of these gamma-quanta at arbitrary distances from those structures. The FermiCORD code system has been benchmarked against similar algorithms based on other code systems and showed a good agreement. The code system has been applied for calculation of the residual dose of the target station for the Mu2e experiment and the results have been compared to approximate dosimetric approaches.

Influence of irradiation dose on laser-induced surface nanostructures on silicon

Energy Technology Data Exchange (ETDEWEB)

Varlamova, Olga [Brandenburgische Technische Universität BTU Cottbus, Platz der Deutschen Einheit 1, 03046 Cottbus (Germany); Cottbus JointLab, Platz der Deutschen Einheit 1, 03046 Cottbus (Germany); Bounhalli, Mourad [Brandenburgische Technische Universität BTU Cottbus, Platz der Deutschen Einheit 1, 03046 Cottbus (Germany); Laboratoire Hubert Curien, Université St. Etienne, Bâtiment F 18 Rue du Professeur Benoît Lauras, 42000 Saint-Etienne (France); Reif, Juergen, E-mail: REIF@TU-COTTBUS.DE [Brandenburgische Technische Universität BTU Cottbus, Platz der Deutschen Einheit 1, 03046 Cottbus (Germany); Cottbus JointLab, Platz der Deutschen Einheit 1, 03046 Cottbus (Germany)

2013-08-01

We report on the dependence of femtosecond laser-induced periodic surface structures on an increase of incident pulse number. On silicon, the patterns evolve from linear, parallel sub-wavelength ripples, grossly perpendicular to the laser polarization, via coalesced wider features parallel to the polarization, to a crater with periodically structured, pillar-like walls. Closer inspection of the patterns indicates that the different features always continue to exhibit reminiscence to the preceding lower-dose patterns, suggesting that, indeed, all patterns can be created by ONE single GENERAL formation process, as in self-organized structure formation, and the different structures/feature sizes are NOT due to DIFFERENT mechanisms.

Influence of irradiation dose on laser-induced surface nanostructures on silicon

International Nuclear Information System (INIS)

Varlamova, Olga; Bounhalli, Mourad; Reif, Juergen

2013-01-01

We report on the dependence of femtosecond laser-induced periodic surface structures on an increase of incident pulse number. On silicon, the patterns evolve from linear, parallel sub-wavelength ripples, grossly perpendicular to the laser polarization, via coalesced wider features parallel to the polarization, to a crater with periodically structured, pillar-like walls. Closer inspection of the patterns indicates that the different features always continue to exhibit reminiscence to the preceding lower-dose patterns, suggesting that, indeed, all patterns can be created by ONE single GENERAL formation process, as in self-organized structure formation, and the different structures/feature sizes are NOT due to DIFFERENT mechanisms.

Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

Science.gov (United States)

Park, Gab-jin; Bae, Soo Hyeon; Park, Wan-Su; Han, Seunghoon; Park, Min-Ho; Shin, Seok-Ho; Shin, Young G; Yim, Dong-Seok

2017-01-01

Purpose A microdose drug–drug interaction (DDI) study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim) and known perpetrators: fluconazole (inhibitor) and rifampin (inducer). For both studies, the microdose (100 μg, cold compound) and the regular dose (20 mg) of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only) of maximum concentration (Cmax) and area under the curve to the last measurement (AUCt) of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro) and 2.68 (regular) for Cmax, and 4.07 (micro), 4.33 (regular) for AUCt. For the induction study, they were 0.26 (micro) and 0.21 (regular) for Cmax, and 0.16 (micro) and 0.15 (regular) for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion Our results may be used as partial evidence that microdose DDI studies may replace regular-dose studies, or at least be used for DDI-screening purposes. PMID:28408803

A combination of low-dose bevacizumab and imatinib enhances vascular normalisation without inducing extracellular matrix deposition.

Science.gov (United States)

Schiffmann, L M; Brunold, M; Liwschitz, M; Goede, V; Loges, S; Wroblewski, M; Quaas, A; Alakus, H; Stippel, D; Bruns, C J; Hallek, M; Kashkar, H; Hacker, U T; Coutelle, O

2017-02-28

Vascular endothelial growth factor (VEGF)-targeting drugs normalise the tumour vasculature and improve access for chemotherapy. However, excessive VEGF inhibition fails to improve clinical outcome, and successive treatment cycles lead to incremental extracellular matrix (ECM) deposition, which limits perfusion and drug delivery. We show here, that low-dose VEGF inhibition augmented with PDGF-R inhibition leads to superior vascular normalisation without incremental ECM deposition thus maintaining access for therapy. Collagen IV expression was analysed in response to VEGF inhibition in liver metastasis of colorectal cancer (CRC) patients, in syngeneic (Panc02) and xenograft tumours of human colorectal cancer cells (LS174T). The xenograft tumours were treated with low (0.5 mg kg -1 body weight) or high (5 mg kg -1 body weight) doses of the anti-VEGF antibody bevacizumab with or without the tyrosine kinase inhibitor imatinib. Changes in tumour growth, and vascular parameters, including microvessel density, pericyte coverage, leakiness, hypoxia, perfusion, fraction of vessels with an open lumen, and type IV collagen deposition were compared. ECM deposition was increased after standard VEGF inhibition in patients and tumour models. In contrast, treatment with low-dose bevacizumab and imatinib produced similar growth inhibition without inducing detrimental collagen IV deposition, leading to superior vascular normalisation, reduced leakiness, improved oxygenation, more open vessels that permit perfusion and access for therapy. Low-dose bevacizumab augmented by imatinib selects a mature, highly normalised and well perfused tumour vasculature without inducing incremental ECM deposition that normally limits the effectiveness of VEGF targeting drugs.

Characterization of the adaptive response to ionizing radiation induced by low doses of X-rays to Vibrio cholerae cells

International Nuclear Information System (INIS)

Basak, Jayasri

1996-01-01

Pretreatment with sublethal doses of X-rays induced an adaptive response in Vibrio cholerae cells as indicated by their greater resistance to the subsequent challenging doses of X-irradiation. The adaptive response was maximum following a pre-exposure dose of 1.7 Gy X-rays and an optimum incubation period of 40 min at 37C. Pre-exposure to a sublethal dose of 1.7 Gy X-rays made the Vibrio cholerae cells 3.38-fold more resistant to the subsequent challenge by X-rays. Pretreatment with a sublethal dose of hydrogen peroxide offered a similar degree of protection to the bacterial cells against subsequent treatment with challenging doses of X-ray radiation. However, exposure of Vibrio cholerae cells to mild heat (42C for 10 min) before X-ray irradiation decreased their survival following X-irradiation

Low dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene

DEFF Research Database (Denmark)

Nielsen, Mads; Raundahl, Jakob; Pettersen, Paola

2009-01-01

Objective: To investigate whether transdermal low dose estradiol treatment induces changes in mammographic density or heterogeneity compared to raloxifene. Secondarily, if these changes relate to changes in bone formation/resorption markers, and if these findings indicate elevation of breast canc...

Non-genotoxic carcinogens: early effects on gap junctions, cell proliferation and apoptosis in the rat

International Nuclear Information System (INIS)

Mally, Angela; Chipman, James Kevin

2002-01-01

Non-genotoxic carcinogens are thought to induce tumour formation by disturbing the balance between cell growth and cell death. Gap junctions (GJ) contribute to the maintenance of tissue homeostasis by allowing the intercellular exchange of growth regulatory signals and potential inhibition of GJ intercellular communication through loss of connexin (Cx) plaques has been shown to be involved in the cancer process. We have investigated the time- and dose-dependent effects of the non-genotoxic hepatocarcinogens Wy-14,643, 2,3,7,8-tetrachlorodibenzo-p-dioxin, methapyrilene and hexachlorobenzene and the male rat kidney carcinogens chloroform, p-dichlorobenzene and d-limonene on gap junction plaque expression in relation to proliferation and apoptosis. With the exception of limonene, all non-genotoxic carcinogens significantly reduced the expression of GJ plaques containing Cx32 in their respective target tissue. No dose-dependent, significant effects were seen in non-target organs. Although alteration of Cx32 expression did not appear to correlate with induction of cell proliferation, out data suggest that the interaction of both processes--interference of GJ coupled with a proliferative stimulus (at the carcinogenic dose)--may be important in non-genotoxic carcinogenesis and provide a potential alert for non-genotoxic carcinogens in short-term toxicity tests

Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

Energy Technology Data Exchange (ETDEWEB)

Scott, Bobby, R., Ph.D.

2003-06-27

OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

Dose-Related Effects of Acetylsalicylic acid (ASA) on Gamma Radiation-Induced Teratogenicity in Pregnant Albino Rats

International Nuclear Information System (INIS)

Ibrahim, M.F.

2013-01-01

Reviews of acetylsalicylic acid (ASA), a widely used nonsteroidal anti- inflammatory drug, has consistently suggested a possible association between prenatal ASA ingestion and adverse effects in the pregnant mothers and their developing fetuses. The objective of the current study was to comprehensively define the effect of relatively low and high doses of ASA (25 mg/kg body wt. and 200 mg/kg body wt. respectively) on gestating rats and their possible impact on the irradiated ones. Therefore 36 pregnant rats were randomly divided into 6 equal groups. Three rat groups were daily orally gavaged from the 7th to the 18th gestational days with: distilled water (Group 1), 25 mg/kg body wt. ASA (Group 2) and 200 mg/kg body wt. ASA (Group 3). The other three groups similarly received the same previous treatments besides 2 Gy whole body gamma irradiation of each, to serve as: Group 4 (distilled water + irradiation), Group 5 (25 mg/kg body wt. ASA + irradiation) and Group 6 (200 mg/kg body wt. ASA + irradiation). All rat groups were sacrificed on the 20th day of pregnancy and the uterine contents were examined. The lower ASA dose (25 mg/kg body wt.) treated group (Group 2) displayed healthy mothers and fetuses whereas that of the higher dose (200 mg/kg body wt.) (Group 3) despite not showing significant maternal or fetal mortalities, yet the intrauterine contents presented fetal developmental disorders including stunted growth and resorption together with some head and limb anomalies including plagiocephaly, marked acampsia and acrocontracture. Meanwhile, results have unexpectedly shown a radioprotective role of the lower ASA dose (25 mg/kg. body wt.) (Group 5) to pregnant rats and their fetuses as inspected by its efficacy in retrieving the radiation induced maternal weight loss together with its noticeable ameliorating effects on the intrauterine lethality of the affected fetuses and their externally detected abnormalities in addition toits effectiveness in retaining some

Corticosteroid effects on ventilator-induced diaphragm dysfunction in anesthetized rats depend on the dose administered

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Decramer Marc

2010-12-01

Full Text Available Abstract Background High dose of corticosteroids has been previously shown to protect against controlled mechanical ventilation (CMV-induced diaphragmatic dysfunction while inhibiting calpain activation. Because literature suggests that the calpain inhibiting effect of corticosteroid depends on the dose administered, we determined whether lower doses of corticosteroids would also provide protection of the diaphragm during CMV. This may be important for patients undergoing mechanical ventilation and receiving corticosteroids. Methods Rats were assigned to controls or to 24 hours of CMV while being treated at the start of mechanical ventilation with a single intramuscular administration of either saline, or 5 mg/kg (low MP or 30 mg/kg (high MP of methylprednisolone. Results Diaphragmatic force was decreased after CMV and this was exacerbated in the low MP group while high MP rescued this diaphragmatic dysfunction. Atrophy was more severe in the low MP group than after CMV while no atrophy was observed in the high MP group. A significant and similar increase in calpain activity was observed in both the low MP and CMV groups whereas the high dose prevented calpain activation. Expression of calpastatin, the endogenous inhibitor of calpain, was decreased in the CMV and low MP groups but its level was preserved to controls in the high MP group. Caspase-3 activity increased in all CMV groups but to a lesser extent in the low and high MP groups. The 20S proteasome activity was increased in CMV only. Conclusions Administration of 30 mg/kg methylprednisolone during CMV protected against CMV-induced diaphragm dysfunction while 5 mg/kg was more deleterious. The protective effect is due mainly to an inhibition of the calpain system through preservation of calpastatin levels and to a lesser extent to a caspase-3 inhibition.

Low dose radiation enhance the anti-tumor effect of high dose radiation on human glioma cell U251

International Nuclear Information System (INIS)

Wang Chang; Wang Guanjun; Tan Yehui; Jiang Hongyu; Li Wei

2008-01-01

Objective: To detect the effect on the growth of human glioma cell U251 induced by low dose irradiation and low dose irradiation combined with large dose irradiation. Methods: Human glioma cell line U251 and nude mice carried with human glioma were used. The tumor cells and the mice were treated with low dose, high dose, and low dose combined high dose radiation. Cells growth curve, MTT and flow cytometry were used to detect the proliferation, cell cycle and apoptosis of the cells; and the tumor inhibition rate was used to assess the growth of tumor in vivo. Results: After low dose irradiation, there was no difference between experimental group and control group in cell count, MTT and flow cytometry. Single high dose group and low dose combined high dose group both show significantly the suppressing effect on tumor cells, the apoptosis increased and there was cell cycle blocked in G 2 period, but there was no difference between two groups. In vivo apparent anti-tumor effect in high dose radiation group and the combining group was observed, and that was more significant in the combining group; the prior low dose radiation alleviated the injury of hematological system. There was no difference between single low dose radiation group and control. Conclusions: There is no significant effect on human glioma cell induced by low dose radiation, and low dose radiation could not induce adaptive response. But in vivo experience, low dose radiation could enhance the anti-tumor effect of high dose radiation and alleviated the injury of hematological system. (authors)

Bayesian estimation of dose rate effectiveness

International Nuclear Information System (INIS)

Arnish, J.J.; Groer, P.G.

2000-01-01

A Bayesian statistical method was used to quantify the effectiveness of high dose rate 137 Cs gamma radiation at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice. The Bayesian approach considers both the temporal and dose dependence of radiation carcinogenesis and total mortality. This paper provides the first direct estimation of dose rate effectiveness using Bayesian statistics. This statistical approach provides a quantitative description of the uncertainty of the factor characterising the dose rate in terms of a probability density function. The results show that a fixed dose from 137 Cs gamma radiation delivered at a high dose rate is more effective at inducing fatal mammary tumours and increasing the overall mortality rate in BALB/c female mice than the same dose delivered at a low dose rate. (author)

Tumor sterilization dose and radiation induced change of the brain tissue in radiotherapy of brain tumors

International Nuclear Information System (INIS)

Yoshii, Yoshihiko; Maki, Yutaka; Takano, Shingo

1987-01-01

Ninety-seven patients with brain tumors (38 gliomas, 26 brain metastases, 18 sellar tumors, 15 others) were treated by cobalt gamma ray or proton radiotherapy. In this study, normal brain injury due to radiation was analysed in terms of time-dose-fractionation (TDF), nominal standard dose (NSD) by the Ellis formula and NeuNSD by a modification in which the N exponent was -0.44 and the T exponent was -0.06. Their calculated doses were analysed in relationship to the normal brain radiation induced change (RIC) and the tumor sterilization dose. All brain tumors with an exception of many patients with brain metastases were received a surgical extirpation subtotally or partially prior to radiotherapy. And all patients with glioma and brain metastasis received also immuno-chemotherapy in the usual manner during radiotherapy. The calculated dose expressed by NeuNSD and TDF showed a significant relationship between a therapeutic dose and a postradiation time in terms of the appearance of RIC. It was suggested that RIC was caused by a dose over 800 in NeuNSD and a dose over 70 in TDF. Furthermore, it was suggested that an aged patient and a patient who had the vulnerable brain tissue to radiation exposure in the irradiated field had the high risk of RIC. On the other hand, our results suggested that the tumor sterilization dose should be over 1,536 NeuNSD and the irradiated method should be further considered in addition to the radiobiological concepts for various brain tumors. (author)

A dose error evaluation study for 4D dose calculations

Science.gov (United States)

Milz, Stefan; Wilkens, Jan J.; Ullrich, Wolfgang

2014-10-01

Previous studies have shown that respiration induced motion is not negligible for Stereotactic Body Radiation Therapy. The intrafractional breathing induced motion influences the delivered dose distribution on the underlying patient geometry such as the lung or the abdomen. If a static geometry is used, a planning process for these indications does not represent the entire dynamic process. The quality of a full 4D dose calculation approach depends on the dose coordinate transformation process between deformable geometries. This article provides an evaluation study that introduces an advanced method to verify the quality of numerical dose transformation generated by four different algorithms. The used transformation metric value is based on the deviation of the dose mass histogram (DMH) and the mean dose throughout dose transformation. The study compares the results of four algorithms. In general, two elementary approaches are used: dose mapping and energy transformation. Dose interpolation (DIM) and an advanced concept, so called divergent dose mapping model (dDMM), are used for dose mapping. The algorithms are compared to the basic energy transformation model (bETM) and the energy mass congruent mapping (EMCM). For evaluation 900 small sample regions of interest (ROI) are generated inside an exemplary lung geometry (4DCT). A homogeneous fluence distribution is assumed for dose calculation inside the ROIs. The dose transformations are performed with the four different algorithms. The study investigates the DMH-metric and the mean dose metric for different scenarios (voxel sizes: 8 mm, 4 mm, 2 mm, 1 mm 9 different breathing phases). dDMM achieves the best transformation accuracy in all measured test cases with 3-5% lower errors than the other models. The results of dDMM are reasonable and most efficient in this study, although the model is simple and easy to implement. The EMCM model also achieved suitable results, but the approach requires a more complex

The influence of non-radiation induced ESR background signal from paraffin-alanine probes for dosimetry in the radiotherapy dose range

International Nuclear Information System (INIS)

Wieser, A.; Lettau, C.; Fill, U.; Regulla, D.F.

1993-01-01

The yield of radicals induced by ionizing radiation in the amino acid alanine and its quantification by ESR spectroscopy has proven excellent reproducibility. Those radicals trapped in the crystal lattice are prevented from recombination providing a thermally very stable system. This allows alanine to be applied as a transfer dosemeter. With paraffin-alanine probes ESR dosimetry can be performed with a standard deviation of ± 0.5% in the dose range from 20 Gy up to 100 kGy. At 1 Gy dose level the error increases to ± 6%. This dose level is three orders of magnitude higher than the calculated detection threshold for alanine with modern X-band ESR spectrometers. It was found that the poor standard deviation at the 1 Gy dose level, is not mainly produced by a bad signal-to-noise ratio but by a variable non-radiation induced ESR background signal from the alanine probes within a batch. In the present study the main sources of error for ESR dosimetry in the dose range below 20 Gy were analyzed. The influences of the production process, UV light and humidity upon the ESR background signal from paraffin-alanine probes were investigated. Measurements are shown indicating a second stable structure of the alanine radical at room temperature. (author)

High doses of L-naloxone but neither D-naloxone nor beta-funaltrexamine prevent hyperthermia-induced seizures in rat pups.

Science.gov (United States)

Laorden, M L; Miralles, F S; Puig, M M

1988-03-01

The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist beta-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40 degrees C showed a gradual increase in body temperature reaching a maximum of 42 +/- 0.1 degrees C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and beta-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.

Exacerbation of benign familial neonatal epilepsy induced by massive doses of phenobarbital and midazolam.

Science.gov (United States)

Maeda, Tomoki; Shimizu, Miki; Sekiguchi, Kazuhito; Ishii, Atsushi; Ihara, Yukiko; Hirose, Shinichi; Izumi, Tatsuro

2014-08-01

Barbiturates and benzodiazepines are the first-line anticonvulsants for neonatal seizures. However, in immature brains, those drugs may lead to paradoxical neuronal excitation. A patient with benign familial neonatal epilepsy developed epileptic encephalopathy after massive doses of phenobarbital that were followed by a continuous infusion of midazolam on postnatal day 3. Electroencephalography revealed rhythmic delta activity in clusters with migrating epileptic foci. After discontinuation of both drugs, the patient's consciousness promptly improved and her electroencephalography normalized on postnatal day 5. This baby developed persistent electroencephalographic seizures due to massive doses of phenobarbital and midazolam. Clinicians should be aware of this anticonvulsant-induced paradoxical neuronal excitation and the uncoupling phenomenon, especially in individuals with benign familial neonatal epilepsy, who have low seizure thresholds. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

Science.gov (United States)

Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

2012-03-01

Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

90Y/90 Sr electron induced damages in an essential eucalyptus oil related to the absorbed dose

International Nuclear Information System (INIS)

Heredia Cardona, J.A.; Diaz Rizo, O.; Martinez Luzardo, F.; Quert, R.

2007-01-01

A good irradiation geometry was achieved in order to carry out the irradiation of an essential eucalyptus oil with a 90 Y/ 90 Sr electron source. The Monte Carlo simulation code MCNP-4C was employed to determine the absorbed doses in this particular experimental configuration. It also helped us to understand which electrons (from an energetic point of view) were responsible for the damages. In order to identify the induced damages, the irradiated samples were studied by mass spectrometry. The obtained results were related to the absorbed doses determined by the computational simulation

Age and dose as determinants of times of appearance of radium-induced osteosarcomas in humans

International Nuclear Information System (INIS)

Stebbings, J.H.; Lucas, H.F.

1983-01-01

Determinants of time-until-tumor for bone sarcomas in US radium cases have been reevaluated. For the 57 measured female bone sarcoma cases exposed to 226 Ra and/or 228 Ra, ages at appearance of tumor are more strongly correlated with radium intake doses than are latency periods. Ages at appearance of tumor increase as initial radium intakes decrease. As many lower dose cases were iatrogenic cases exposed in mid-adult life, rather than about age 22 as for the dial worker cases, these results may be artifactual, resulting from an increased susceptability to sarcoma induction at older ages. Alternatively the time of appearance of a sarcoma may be in part directly determined by age. Both explanations find support in the literature. These results suggest that 226 228 Ra-induced bone sarcomas do have an expression period. The downturn in sarcoma incidence at very high doses may result from truncation of the expression period on its early side by the minimum induction period

Natural radioactivity contents in tobacco and radiation dose induced from smoking

International Nuclear Information System (INIS)

Shousha, H. A.; Ahmad, F.

2012-01-01

One of the causative factors for cancer-inducing mechanisms in humans is radioactive elements present in tobacco leaves used in the manufacture of cigarettes. Smoking of tobacco and its products increases the internal intake and radiation dose due to naturally occurring radionuclides that are considered to be one of the most significant causes of lung cancer. In this work, different commercial types of cigarettes, cigar and moassel were collected from market. Naturally occurring radionuclides 226 Ra and 214 Bi ( 238 U series), 228 Ac and 228 Ra ( 232 Th series), 40 K and man-made 137 Cs were measured in tobacco using gamma-ray spectrometer. Results show that the average concentrations of 238 U, 232 Th and 40 K were 4.564, 3.940 and 1289.53 Bq kg -1 , respectively. This reflects their origin from the soil by root uptake and fertilisers used in the cultivation of tobacco plants. Concentration of 137 Cs was 0.348 Bq kg -1 due to root uptake or deposition onto the leaf foliage. For smokers, the annual effective dose due to inhalation of 238 U varied from 49.35 to 139.40 μSv -1 (average 104.27 μSv y -1 ), while of 232 Th from 23.86 to 111.06 μSv y -1 (average 65.52 μSv y -1 ). The annual effective dose resulting from 137 Cs was varied from 10.96 to 24.01 nSv y -1 (average 19.41 nSv y -1 ). (authors)

Low doses of dextromethorphan attenuate morphine-induced rewarding via the sigma-1 receptor at ventral tegmental area in rats.

Science.gov (United States)

Chen, Shiou-Lan; Hsu, Kuei-Ying; Huang, Eagle Yi-Kung; Lu, Ru-Band; Tao, Pao-Luh

2011-09-01

Chronic use of morphine causes rewarding and behavioral sensitization, which may lead to the development of psychological craving. In our previous study, we found that a widely used antitussive dextromethorphan (known as a low affinity NMDA receptor antagonist), at doses of 10-20 mg/kg (i.p.), effectively decreased morphine rewarding in rats. In this study, we further investigated the effects and mechanisms of low doses of DM (μg/kg range) on morphine rewarding and behavioral sensitization. A conditioned place preference test was used to determine the rewarding and a locomotor activity test was used to determine the behavioral sensitization induced by the drug(s) in rats. When a low dose of DM (3 or 10 μg/kg, i.p.) was co-administered with morphine (5 mg/kg, s.c.), the rewarding effect, but not behavioral sensitization, induced by morphine was inhibited. The inhibiting effect of DM could be blocked by systemically administering a sigma-1 receptor antagonist, BD1047 (3 mg/kg, i.p.). When BD1047 (5 nmole/site) was locally given at the VTA, it also blocked the effects of a low dose of DM in inhibiting morphine rewarding. Our findings suggest that the activation of the sigma-1 receptor at the VTA may be involved in the mechanism of low doses of DM in inhibiting the morphine rewarding effect and the possibility of using extremely low doses of DM in treatment of opioid addiction in clinics. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Low-dose radiation (LDR) induces hematopoietic hormesis: LDR-induced mobilization of hematopoietic progenitor cells into peripheral blood circulation.

Science.gov (United States)

Li, Wei; Wang, Guanjun; Cui, Jiuwei; Xue, Lu; Cai, Lu

2004-11-01

The aim of this study was to investigate the stimulating effect of low-dose radiation (LDR) on bone marrow hematopoietic progenitor cell (HPC) proliferation and peripheral blood mobilization. Mice were exposed to 25- to 100-mGy x-rays. Bone marrow and peripheral blood HPCs (BFU-E, CFU-GM, and c-kit+ cells) were measured, and GM-CSF, G-CSF, and IL-3 protein and mRNA expression were detected using ELISA, slot blot hybridization, and Northern blot methods. To functionally evaluate LDR-stimulated and -mobilized HPCs, repopulation of peripheral blood cells in lethally irradiated recipients after transplantation of LDR-treated donor HPCs was examined by WBC counts, animal survival, and colony-forming units in the recipient spleens (CFUs-S). 75-mGy x-rays induced a maximal stimulation for bone marrow HPC proliferation (CFU-GM and BFU-E formation) 48 hours postirradiation, along with a significant increase in HPC mobilization into peripheral blood 48 to 72 hours postradiation, as shown by increases in CFU-GM formation and proportion of c-kit+ cells in the peripheral mononuclear cells. 75-mGy x-rays also maximally induced increases in G-CSF and GM-CSF mRNA expression in splenocytes and levels of serum GM-CSF. To define the critical role of these hematopoietic-stimulating factors in HPC peripheral mobilization, direct administration of G-CSF at a dose of 300 microg/kg/day or 150 microg/kg/day was applied and found to significantly stimulate GM-CFU formation and increase c-kit+ cells in the peripheral mononuclear cells. More importantly, 75-mGy x-rays plus 150 microg/kg/day G-CSF (LDR/150-G-CSF) produced a similar effect to that of 300 microg/kg/day G-CSF alone. Furthermore, the capability of LDR-mobilized donor HPCs to repopulate blood cells was confirmed in lethally irradiated recipient mice by counting peripheral WBC and CFUs-S. These results suggest that LDR induces hematopoietic hormesis, as demonstrated by HPC proliferation and peripheral mobilization, providing a

ACDOS2: a code for neutron-induced activities and dose rates

International Nuclear Information System (INIS)

Ruby, L.; Keney, G.S.; Lagache, J.C.

1981-10-01

In order to anticipate problems from the radioactivation of neutral beam sources as a result of testing, a code has been developed which calculates both the radioactivities produced and the dose rates resulting therefrom. The code ACDOS2 requires neutron source strength and spectral distribution as input, or alternately, the source strength can be calculated internally from an input of neutral beam source parameters. A variety of simple geometries can be specified, and up to 12 times of interest following the shutdown of the neutron source. Radiation attenuating and daughter radioactivities are treated accurately. ACDOS2 is also of use for neutron-induced radioactivation problems involving accelerators, fusion reactors, or fission reactors

Cytogenetic Effects of Low Dose Radiation in Mammalian Cells Analysis of the Phenomenon Hypersensitivity and Induced Radioresistence

CERN Document Server

Shmakova, N L; Nasonova, E A; Krasavin, E A; Rsjanina, A V

2001-01-01

The induction of cytogenetic damage after irradiation of chinese hamster cells and human melanoma cells within dose range 1-200 cGy was studied. The anaphase and metaphase analysis of chromosome damage and micronuclei test were applied. The hypersensitivity (HRS) at doses below 20 cGy and the increased radioresistence at higher doses (IR) were shown with all cytogenetic criteria for both cell lines. The phenomenon of HRS/IR was reproduced in synchronic as well as in asynchronic population of chinese hamster cells. This fact shows that HRS was caused by high radiosensitivity of all cells and can not be explained by any differential sensitivity of cells in different phases of the cell cycle. So it was supposed that the increasing radioresistence is determined by the inclusion of the inducible repair processes in all cells. This conclusion agress with the fact that there was no evidence of HRS on dose-effect curves and that some part of pre-existent damage was repaired after preliminary irradiation with low dose...

Editorial: dose-dependent ZnO particle-induced acute phase response in humans warrants re-evaluation of occupational exposure limits for metal oxides

DEFF Research Database (Denmark)

Vogel, Ulla Birgitte; Cassee, Flemming R.

2018-01-01

in autonomic imbalance and particle-induced pulmonary inflammation and acute phase response.The acute phase response is the systemic response to acute and chronic inflammatory states caused by for example bacterial infection, virus infection, trauma and infarction. It is characterized by differential...... studies and SAA has been causally related to the formation of plaques in the aorta in animal studies.In a recent paper in Particle and Fibre Toxicology, Christian Monse et al. provide evidence that inhalation of ZnO nanoparticles induces dose-dependent acute phase response in humans at dose levels well...

A double-blind, randomized, pilot dose-finding study of maca root (L. meyenii) for the management of SSRI-induced sexual dysfunction.

Science.gov (United States)

Dording, Christina M; Fisher, Lauren; Papakostas, George; Farabaugh, Amy; Sonawalla, Shamsah; Fava, Maurizio; Mischoulon, David

2008-01-01

We sought to determine whether maca, a Peruvian plant, is effective for selective-serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction. We conducted a double-blind, randomized, parallel group dose-finding pilot study comparing a low-dose (1.5 g/day) to a high-dose (3.0 g/day) maca regimen in 20 remitted depressed outpatients (mean age 36+/-13 years; 17 women) with SSRI-induced sexual dysfunction. The Arizona Sexual Experience Scale (ASEX) and the Massachusetts General Hospital Sexual Function Questionnaire (MGH-SFQ) were used to measure sexual dysfunction. Ten subjects completed the study, and 16 subjects (9 on 3.0 g/day; 7 on 1.5 g/day) were eligible for intent-to-treat (ITT) analyses on the basis of having had at least one postbaseline visit. ITT subjects on 3.0 g/day maca had a significant improvement in ASEX (from 22.8+/-3.8 to 16.9+/-6.2; z=-2.20, P=0.028) and in MGH-SFQ scores (from 24.1+/-1.9 to 17.0+/-5.7; z=-2.39, P=0.017), but subjects on 1.5 g/day maca did not. Libido improved significantly (PMaca was well tolerated. Maca root may alleviate SSRI-induced sexual dysfunction, and there may be a dose-related effect. Maca may also have a beneficial effect on libido.

No indications of an enhanced UV-light-induced unscheduled DNA synthesis in splenocytes of mice following a low-dose irradiation in vivo or in vitro

International Nuclear Information System (INIS)

Wojcik, A.; Seemayer, C.A.; Mueller, W.U.; Streffer, C.

1995-01-01

One of the open questions regarding the adaptive response to ionizing radiation is whether it can be induced in G 0 lymphocytes. In the majority of experiments in which an adaptive response in G 0 lymphocytes was observed, the adapting dose was applied in vivo. In order to investigate whether there is some in vivo component of adaptive response, mouse splenocytes of the C57BL/6 strain were irradiated with 0.1 Gy x-rays either in vivo or in vitro, and their UV-light-induced unscheduled DNA synthesis (UDS) levels were determined autoradiographically. An augmented UV-light-induced UDS following an adapting dose applied in vivo has previously been described by several authors in splenocytes of C57BL/6 mice, indicating that the adapting dose enhanced the DNA repair capacity of lymphocytes. In the present investigation, however, no evidence of an adaptive response could be seen regardless of whether the adapting dose was given in vivo or in vitro. Those results present a further indication for the fact that the adaptive response to ionizing radiation is not always inducible, even in lymphocytes of an inbred mouse strain in which its existence has been reported before. (orig.)

The MARS15-based FermiCORD code system for calculation of the accelerator-induced residual dose

Science.gov (United States)

Grebe, A.; Leveling, A.; Lu, T.; Mokhov, N.; Pronskikh, V.

2018-01-01

The FermiCORD code system, a set of codes based on MARS15 that calculates the accelerator-induced residual doses at experimental facilities of arbitrary configurations, has been developed. FermiCORD is written in C++ as an add-on to Fortran-based MARS15. The FermiCORD algorithm consists of two stages: 1) simulation of residual doses on contact with the surfaces surrounding the studied location and of radionuclide inventories in the structures surrounding those locations using MARS15, and 2) simulation of the emission of the nuclear decay γ-quanta by the residuals in the activated structures and scoring the prompt doses of these γ-quanta at arbitrary distances from those structures. The FermiCORD code system has been benchmarked against similar algorithms based on other code systems and against experimental data from the CERF facility at CERN, and FermiCORD showed reasonable agreement with these. The code system has been applied for calculation of the residual dose of the target station for the Mu2e experiment and the results have been compared to approximate dosimetric approaches.

Regional changes in brain 2-14C-deoxyglucose uptake induced by convulsant and non-convulsant doses of lindane

International Nuclear Information System (INIS)

Sanfeliu, C.; Sola, C.; Camon, L.; Martinez, E.; Rodriguez-Farre, E.

1990-01-01

Lindane-induced dose- and time-related changes in regional 2-14C-deoxyglucose (2-DG) uptake were examined in 59 discrete rat brain structures using the 2-DG autoradiographic technique. At different times (0.5-144 hr) after administration of a seizure-inducing single dose of lindane (60 mg/kg), 2-DG uptake was significantly increased in 18 cortical and subcortical regions mainly related to the limbic system (e.g., Ammon's horn, dentate gyrus, septal nuclei, nucleus accumbens, olfactory cortex) and extrapyramidal and sensory-motor areas (e.g., cerebellar cortex, red nucleus, medial vestibular nucleus). There was also a significant increase in superior colliculus layer II. In addition, significant decreases occurred in a group of 6 regions (e.g., auditory and motor cortices). Non-convulsing animals treated with the same dose of lindane showed a regional pattern of 2-DG uptake less modified than the convulsant group. A non-convulsant single dose of lindane (30 mg/kg) also modified significantly the 2-DG uptake (0.5-24 hr) in some brain areas. Although the various single doses of lindane tested produced different altered patterns of brain 2-DG uptake, some structures showed a similar trend in their modification (e.g., superior colliculi and accumbens, raphe and red nuclei). Repeated non-convulsant doses of lindane produced defined and long-lasting significant elevations of 2-DG uptake in some subcortical structures. Considering the treated groups all together, 2-DG uptake increased significantly in 26 of the 59 regions examined but only decreased significantly in 9 of them during the course of lindane effects. This fact can be related to the stimulant action described for this neurotoxic agent. The observed pattern provides a descriptive approach to the functional alterations occurring in vivo during the course of lindane intoxication

High doses of salicylate causes prepulse facilitation of onset-gap induced acoustic startle response.

Science.gov (United States)

Sun, Wei; Doolittle, Lauren; Flowers, Elizabeth; Zhang, Chao; Wang, Qiuju

2014-01-01

Prepulse inhibition of acoustic startle reflex (PPI), a well-established method for evaluating sensorimotor gating function, has been used to detect tinnitus in animal models. Reduced gap induced PPI (gap-PPI) was considered as a sign of tinnitus. The silent gap used in the test contains both onset and offset signals. Tinnitus may affect these cues differently. In this experiment, we studied the effects of a high dose of salicylate (250 mg/kg, i.p.), an inducer of reversible tinnitus and sensorineural hearing loss, on gap-PPI induced by three different gaps: an onset-gap with 0.1 ms onset and 25 ms offset time, an offset-gap with 25 ms onset and 0.1 ms offset time, and an onset-offset-gap with 0.1 ms onset and offset time. We found that the onset-gaps induced smaller inhibitions than the offset-gaps before salicylate treatment. The offset-gap induced PPI was significantly reduced 1-3h after salicylate treatment. However, the onset-gap caused a facilitation of startle response. These results suggest that salicylate induced reduction of gap-PPI was not only caused by the decrease of offset-gap induced PPI, but also by the facilitation induced by the onset-gap. Since the onset-gap induced PPI is caused by neural offset response, our results suggest that salicylate may cause a facilitation of neural response to an offset acoustical signal. Treatment of vigabatrin (60 mg/kg/day, 14 days), which elevates the GABA level in the brain, blocked the offset-gap induced PPI and onset-gap induced facilitation caused by salicylate. These results suggest that enhancing GABAergic activities can alleviate salicylate induced tinnitus. Published by Elsevier B.V.

Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazine- induced reproductive toxicity in adult male Albino rats.

Science.gov (United States)

Abdel Aziz, Rabie L; Abdel-Wahab, Ahmed; Abo El-Ela, Fatma I; Hassan, Nour El-Houda Y; El-Nahass, El-Shaymaa; Ibrahim, Marwa A; Khalil, Abdel-Tawab A Y

2018-06-01

This study aimed to determine the protective effects of co-administration of Quercetin (QT) or l-Carnitine (LC) against the oxidative stress induced by Atrazine (ATZ) in the reproductive system of intact male Albino rats. 36 rats were divided equally into 6 groups. Rats in the control negative "CNT" group received 1.5 ml distilled water for 21 days. All rats in the other groups received ATZ (120 mg/kg bw) through gavage. Groups 3 and 4 were co-administered with either low or high dose of QT (10 "ATZLQT" and 50 "ATZHQT" mg/kg bw, respectively). Groups 5 and 6 were co-administered with either low or high dose of LC (200 "ATZLLC" and 400 "ATZHLC" mg/kg bw, respectively). At the end of the experiment, animals were sacrificed and all samples were collected. ATZ significantly increased serum level of malondialdehyde (MDA) and decreased total antioxidant capacity (TAC). Also, ATZ increased significantly the sperm cell abnormalities and reduced both testicular IgA and serum testosterone levels. Testicular DNA laddering % and CYP17A1 mRNA expression were significantly reduced in ATZ group. Interestingly, co-administration with low dose QT or different doses of LC succeeded to counteract the negative toxic effects of ATZ on serum oxidative stress indicators, serum testosterone levels, testicular IgA level and improved testicular CYP17A1 mRNA expression. In conclusion, QT in low dose and LC in both low and high doses exerted a significant protective action against the reproductive toxicity of ATZ, while higher dose of QT failed induce immune-stimulant effect against ATZ in adult male Albino rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

The dependence of the magnitude of induced adaptive responseon on the dose of pre-irradiation of cultured human lymphocytes under the optimum irradiation time scheme

International Nuclear Information System (INIS)

Mortazavi, S.M.J.; Mozdarani, H.

2000-01-01

Human lymphocytes exposed to low doses of X-rays, become less susceptible to the induction of chromosome aberrations by subsequent exposure to high doses of X-rays. This has been termed the radioadaptive response. One of the most important questions in the adaptive response studies was that of the possible existence of an optimum adapting dose. Early experiments indicated that this response could be induced by low doses of X-rays from 1 cGy to 20 cGy. Recently, it has been interestingly shown that the time scheme of exposure to adapting and challenge doses plays an important role in determination of the magnitude of the induced adaptive response. In this study, using the optimum irradiation time scheme (24-48), we have monitored the cytogenetic endpoint of chromosome aberrations to assess the magnitude of adaptation to ionizing radiation in the cultured human lymphocytes. Lymphocytes were pre-exposed to an adapting dose of 1-20 cGy at 24 hours, before an acute challenge dose of 1 or 2 Gy at 48 hours. Cells were fixed at 54 hours. Lymphocytes, which were pretreated with 5 as well as 10 cGy adapting doses, had significantly fewer chromosome aberrations. In spite of the fact that lymphocytes of some of our blood donors which were pre-treated with 1 or 20 cGy adapting doses, showed an adaptive response, the pooled data (all donors) indicated that such an induction of adaptive response can not be observed in these lymphocytes. The overall pattern of the induced adaptive response, indicated that in human lymphocyte (at least under the above mentioned irradiation scheme), 5 cGy and 10 cGy adapting doses are the optimum doses. (author)

Low-dose Norfloxacin-treated leptospires induce less IL-1β release in J774A.1 cells following discrepant leptospiral gene expression.

Science.gov (United States)

Cao, Yongguo; Xie, Xufeng; Zhang, Wenlong; Wu, Dianjun; Tu, Changchun

2018-06-01

Currently, accumulating evidence is challenging subtherapeutic therapy. Low-dose Norfloxacin (Nor) has been reported to suppress the immune response and worsen leptospirosis. In this study, we investigated the influence of low-dose Nor (0.03 μg/ml, 0.06 μg/ml, 0.125 μg/ml) on leptospiral gene expression and analyzed the immunomodulatory effects of low-dose Nor-treated leptospires in J774A.1 cells. To study the expression profiles of low-dose Nor-treated leptospires, we chose LipL71/LipL21 as reference genes determined by the geNorm applet in this experiment. The results showed that low-dose Nor up-regulated the expression of FlaB and inhibited the expression of 16S rRNA, LipL32, LipL41, Loa22, KdpA, and KdpB compared with the untreated leptospires. These results indicated that low-dose Nor could regulate leptospiral gene expression. Using RT-PCR, the gene expression of IL-1β and TNF-α in J774A.1 cells was detected. Nor-treated leptospires induced higher expression levels of both IL-1β and TNF-α. However, when analyzed by ELISA, the release of mature IL-1β was reduced compared with that observed in cells induced with no Nor-treated leptospires, although the TNF-α protein level showed no significant change. Our study indicated that the gene expression of leptospires could be modulated by low-dose Nor, which induced less IL-1β release in J774A.1 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect

International Nuclear Information System (INIS)

Furlong, Hayley; Mothersill, Carmel; Lyng, Fiona M.; Howe, Orla

2013-01-01

Highlights: ► Molecular mechanisms involved in the production of a radiation induced bystander effect are not well known. ► We investigate gene expression changes in apoptotic genes in both direct and bystander responses. ► We demonstrate initiation of the apoptotic cascade in a bystander response. ► Lower doses reveal a specific but differential response related to apoptosis compared to higher doses. - Abstract: It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05 Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5 Gy dose point and genes were not always expressed within 1 h but were sometimes expressed 24 h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05 Gy and 0.5 Gy at both time points therefore not

Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect

Energy Technology Data Exchange (ETDEWEB)

Furlong, Hayley, E-mail: hayley.furlong@dit.ie [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Mothersill, Carmel [Medical Physics and Applied Radiation Sciences, Nuclear Research Building, 1280 Hamilton, Ontario L8S 4K1 (Canada); Lyng, Fiona M. [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Howe, Orla [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland)

2013-01-15

Highlights: ► Molecular mechanisms involved in the production of a radiation induced bystander effect are not well known. ► We investigate gene expression changes in apoptotic genes in both direct and bystander responses. ► We demonstrate initiation of the apoptotic cascade in a bystander response. ► Lower doses reveal a specific but differential response related to apoptosis compared to higher doses. - Abstract: It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05 Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5 Gy dose point and genes were not always expressed within 1 h but were sometimes expressed 24 h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05 Gy and 0.5 Gy at both time points therefore not

Computational model of dose response for low-LET-induced complex chromosomal aberrations

International Nuclear Information System (INIS)

Eidelman, Y.A.; Andreev, S.G.

2015-01-01

Experiments with full-colour mFISH chromosome painting have revealed high yield of radiation-induced complex chromosomal aberrations (CAs). The ratio of complex to simple aberrations is dependent on cell type and linear energy transfer. Theoretical analysis has demonstrated that the mechanism of CA formation as a result of interaction between lesions at a surface of chromosome territories does not explain high complexes-to-simples ratio in human lymphocytes. The possible origin of high yields of γ-induced complex CAs was investigated in the present work by computer simulation. CAs were studied on the basis of chromosome structure and dynamics modelling and the hypothesis of CA formation on nuclear centres. The spatial organisation of all chromosomes in a human interphase nucleus was predicted by simulation of mitosis-to-interphase chromosome structure transition. Two scenarios of CA formation were analysed, 'static' (existing in a nucleus prior to irradiation) centres and 'dynamic' (formed in response to irradiation) centres. The modelling results reveal that under certain conditions, both scenarios explain quantitatively the dose-response relationships for both simple and complex γ-induced inter-chromosomal exchanges observed by mFISH chromosome painting in the first post-irradiation mitosis in human lymphocytes. (authors)

Comparative studies of dose-response curves for recessive lethal mutations induced by ethylnitrosourea in spermatogonia and in spermatozoa of Drosophila melanogaster

Energy Technology Data Exchange (ETDEWEB)

Yoshikawa, I.; Ayaki, T.; Ohshima, K.

1984-01-01

Induction of recessive lethal mutation by N-ethyl-N-nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa in Drosophila melanogaster. ENU (0.03, 0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. When plotted against absorbed doses of ENU, the observed frequencies to recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU-induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in spermatogonia.

Radiation-induced polymerization of water-saturated styrene in a wide range of dose rate

International Nuclear Information System (INIS)

Takezaki, J.; Okada, T.; Sakurada, I.

1978-01-01

Radiation-induced polymerization of water-saturated styrene (water content 3.5 x 10 -2 mole/liter) was carried out in a wide range of dose rate between 1.2 x 10 3 and 1.8 x 10 7 rad/sec, and compared with the polymerization of the moderately dried styrene (water content 3.2 x 10 -3 mole/liter). Molecular weight distribution curves of the polymerization products showed that they were generally consisted of four parts, namely, oligomers, radical, cationic, and super polymers. Contributions of the four constituents to the polymerization and the number average degrees of polymerization (DP) of the four kinds of polymers were calculated by the graphical analysis of the curves. The rate of radical polymerization and DP of radical polymers are independent of the water content; the dose rate dependences of the polymerization rate and DP agree with the well known square root and inverse square root laws, respectively, of the radical polymerization of styrene. The rate of ionic polymerization is directly proportional to the dose rate, but it decreases, at a given dose rate, inversely proportional to the water content of styrene. DP of ionic polymer is independent of the dose rate but decreases with increasing water content. The super polymer of DP about 10 4 is not formed in the case of the moderately dried styrene. G values for the initiating radical and ion formation are calculated to be independently of the dose rate and water content, 0.66 and 0.027, respectively. It was suggested that oligomer was formed in the early stage by the interaction of cation with anion and only those cations which had survived underwent polymerization. 10 figures, 4 tables

Effect of dose of gamma-rays and ethylmethane sulphonate on the germination and survival of induced mutations in pigeonpea

Energy Technology Data Exchange (ETDEWEB)

Premsekar, S [Central Inst. for Cotton Research, Coimbatore (India). Regional Station; Appadurai, R [Tamil Nadu Agricultural Univ., Coimbatore (India)

1981-06-01

The LD/sub 50/ values for germination and survival of the induced mutants (M/sub 1/) of pigeonpea (Cajanus cajan (Linn.) Millsp.) were attained with 20 and 15 krad when gamma-rays were used, and 30 and 40 mM concentration when EMS was used. In the combination treatments the half-kill dose for germination and survival was reached even at the low dose combination of 5 krad gamma-ray + 20 mM EMS. Higher doses resulted in lower pollen and seed fertility. The sterility was much enhanced in the combined treatments. The number of pods, seed yield and weight of seeds could be stimulated with 10 and 15 krad doses of gamma-rays and 20 mM of EMS. In combination treatments such a stimulatory effect was noticed in seed weight only.

The repair of low dose UV light-induced damage to human skin DNA in condition of trace amount Mg 2+

Science.gov (United States)

Gao, Fang; Guo, Zhouyi; Zheng, Changchun; Wang, Rui; Liu, Zhiming; Meng, Pei; Zhai, Juan

2008-12-01

Ultraviolet light-induced damage to human skin DNA was widely investigated. The primary mechanism of this damage contributed to form cyclobutane pyrimidine dimmers (CPDs). Although the distribution of UV light-induced CPDs within a defined sequence is similar, the damage in cellular environment which shields the nuclear DNA was higher than that in organism in apparent dose. So we use low UVB light as main study agent. Low dose UV-irradiated HDF-a cells (Human Dermal Fibroblasts-adult cells) which is weaker than epidermic cells were cultured with DMEM at different trace amount of Mg2+ (0mmol/L , 0.1mmol/L , 0.2mmol/L, 0.4mmol/L, 0.8mmol/L, 1.2mmol/L) free-serum DMEM and the repair of DNA strands injured were observed. Treat these cells with DNA strand breaks detection, photoproducts detection and the repair of photoproducts detection. Then quantitate the role of trace amount Mg2+ in repair of UV light-induced damage to human skin. The experiment results indicated that epidermic cells have capability of resistance to UV-radiation at a certain extent. And Mg2+ can regulate the UV-induced damage repair and relative vitality. It can offer a rationale and experiment data to relieve UV light-induced skin disease.

Radiation induced wheat-rye chromosomal translocations in triticale. Optimizing the dose using fluorescence in situ hybridization

International Nuclear Information System (INIS)

Ahmad, F.; Comeau, A.; Chen, Q.; Collin, J.; St-Pierre, C.A.

2000-01-01

Fluorescent in situ hybridization (FISH) was utilized to monitor the level of ionizing radiation ( 60 Co source) in their ability to cause intra- and intergeneric chromosomal aberrations in triticale seeds. Seeds were irradiated with 0, 20, 50, 100, 200, 300, 400, 500 and 1000 Gy doses. The root growth of irradiated seeds was greatly inhibited at 200 Gy and above. Various types of aberrations including wheat-rye, wheat-wheat, rye-rye, wheat-rye-wheat, rye-wheat-rye translocations and acentric fragments with or without translocations were observed. There was a consistent increase in proportion of aberrations per cell with an increase in radiation dose. It was concluded that for an optimal level of chromosomal translocation and least number of acentric fragments, a 20 Gy dose was quite sufficient for inducing a desirable level of wheat-rye chromosomal translocations. The excellent efficiency and importance of utilizing FISH in such studies of alien-introgression via chromosomal translocations are discussed. (author)

Radiation induced wheat-rye chromosomal translocations in triticale. Optimizing the dose using fluorescence in situ hybridization

Energy Technology Data Exchange (ETDEWEB)

Ahmad, F. [Brandon Univ., Manitoba (Canada); Comeau, A.; Chen, Q.; Collin, J.; St-Pierre, C.A.

2000-03-01

Fluorescent in situ hybridization (FISH) was utilized to monitor the level of ionizing radiation ({sup 60}Co source) in their ability to cause intra- and intergeneric chromosomal aberrations in triticale seeds. Seeds were irradiated with 0, 20, 50, 100, 200, 300, 400, 500 and 1000 Gy doses. The root growth of irradiated seeds was greatly inhibited at 200 Gy and above. Various types of aberrations including wheat-rye, wheat-wheat, rye-rye, wheat-rye-wheat, rye-wheat-rye translocations and acentric fragments with or without translocations were observed. There was a consistent increase in proportion of aberrations per cell with an increase in radiation dose. It was concluded that for an optimal level of chromosomal translocation and least number of acentric fragments, a 20 Gy dose was quite sufficient for inducing a desirable level of wheat-rye chromosomal translocations. The excellent efficiency and importance of utilizing FISH in such studies of alien-introgression via chromosomal translocations are discussed. (author)

Low level dose induced chromosome aberrations in human blood lymphocytes

International Nuclear Information System (INIS)

Pohl-Rueling, J.

1992-01-01

Unstable structural aberrations in chromosomes of human blood lymphocytes cannot be used as biological dosemeters in the low dose range, when extrapolating from high doses using a linear dose response, as required by the original formula of the dual radiation action theory. A survey is given of experimental dose-response curves of chromosome aberrations, obtained in investigations not only by this institute, in cooperation with many other laboratories, but also by various authors in different areas of the world. The results are not compatible with the predicted linear dose relationships at in vivo dose ranges up to 30 mGy.y -1 . The aberration frequencies rise sharply with dose within the normal environmental exposure up to about twice that level. At higher doses, aberration frequencies increase less rapidly and reach a plateau. Some in vitro experiments of various authors with higher doses of low LET radiations, up to about 400 mGy have found dose responses with steps. (author)

Reversal of rocuronium-induced (1.2 mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1).

NARCIS (Netherlands)

Molina, A.L.; Boer, H.D. de; Klimek, M.; Heeringa, M.; Klein, J.

2007-01-01

Sugammadex is the first selective relaxant binding agent and reverses rocuronium-induced neuromuscular block. A case is reported in which a patient accidentally received a high dose of sugammadex (40 mg kg-1) to reverse a rocuronium-induced (1.2 mg kg-1) profound neuromuscular block. A fast and

Effects of small radiation doses

International Nuclear Information System (INIS)

Fuchs, G.

1986-01-01

The term 'small radiation dosis' means doses of about (1 rem), fractions of one rem as well as doses of a few rem. Doses like these are encountered in various practical fields, e.g. in X-ray diagnosis, in the environment and in radiation protection rules. The knowledge about small doses is derived from the same two forces, on which the radiobiology of human beings nearly is based: interpretation of the Hiroshima and Nagasaki data, as well as the experience from radiotherapy. Careful interpretation of Hiroshima dates do not provide any evidence that small doses can induce cancer, fetal malformations or genetic damage. Yet in radiotherapy of various diseases, e.g. inflammations, doses of about 1 Gy (100 rad) do no harm to the patients. According to a widespread hypothesis even very small doses may induce some types of radiation damage ('no threshold'). Nevertheless an alternative view is justified. At present no decision can be made between these two alternatives, but the usefullness of radiology is definitely better established than any damage calculated by theories or extrapolations. Based on experience any exaggerated fear of radiations can be met. (author)

Progress report, September 1, 1975--April 1, 1976

International Nuclear Information System (INIS)

Borek, E.

1976-01-01

Hypermethylation of the DNA of mammalian cells exposed to uv irradiation was demonstrated. The extent of hypermethylation is a function of the log of the uv dose. The synthesis in vitro of a specific protein, ovalbumin, is potentiated by the addition of tRNAs from the oviduct of mature laying hens or from the oviduct of immature chicks which have been previously stimulated by estrogen. Ethionine, a hepatocarcinogen in female rats, can simulate the effect of an estrogen, both cytological and in ovalbumin synthesizing capacity, in the oviduct of the immature chick

1090 nm infrared radiation at close to threshold dose induces cataract with a time delay.

Science.gov (United States)

Yu, Zhaohua; Schulmeister, Karl; Talebizadeh, Nooshin; Kronschläger, Martin; Söderberg, Per G

2015-03-01

To investigate whether infrared radiation (IRR)-induced cataract is instant or is associated with a time delay between the exposure and the onset of lens light scattering after an exposure to just above threshold dose. Six-weeks-old albino Sprague-Dawley female rats were unilaterally exposed to 197 W/cm2 IRR at 1090 nm within the dilated pupil. In the first experiment, the animals were exposed with four exposure times of 5, 8, 13 and 20 second, respectively. At 24 hr after exposure, the light scattering in both exposed and contralateral not exposed lenses was measured. Based on the first experiment, four postexposure time groups were exposed unilaterally to 1090 nm IRR of 197 W/cm2 for 8 second. At 6, 18, 55 and 168 hr after exposure, the light scattering in both lenses was measured. A 197 W/cm2 IRR-induced light scattering in the lens with exposures of at least 8 second. Further, after exposure to IRR of 197 W/cm2 for 8 second, the light-scattering increase in the lens was delayed approximately 16 hr after the exposure. There is a time delay between the exposure and the onset of cataract after exposure to close to threshold dose implicating that either near IRR cataract is photochemical or there is a time delay in the biological expression of thermally induced damage. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Radiation-induced strand-breaks and DNA-protein crosslinks depend predominantly on the dose, oxygen concentration and repair time

International Nuclear Information System (INIS)

Wheeler, K.T.; Miyagi, Y.; Zhang, H.

1995-01-01

It has been known for many years that the DNA damage produced by ionizing radiation depends upon the oxygen concentration around the DNA. For example, the number of DNA strand-breaks (SBs) formed per unit dose decreases at low oxygen concentrations, and the number of DNA-protein crosslinks formed per unit dose increases at low oxygen concentrations. If radiation-induced SBs and DPCs are to be useful for detecting and/or quantifying hypoxic cells in solid tumors, the formation of these lesions must depend predominantly on the oxygen concentration around the DNA. All other physical, biological, and physiological factors must either be controllable or have little influence on the assay used to measure these lesions. This paper is a summary of the authors' recent experiments to determine if the radiation-induced SBs and DPCs measured by alkaline elution may be used to estimate the hypoxic fraction or fractional hypoxic volume of solid tumors

Possibilities of the reduction of a dose of metronidazole during irradiation of tumor with subsequent induced hyperglycemia

International Nuclear Information System (INIS)

Vinskaya, N.P.; Voloshina, E.A.; Kozin, S.V.

1989-01-01

The therapeutic efficacy of a scheme of polyradiomodification with metronidazole (MZ) administration was investigated in experiments on mice with Ehrlich carcinoma before local irradiation of tumors and with subsequent induced hyperglycemia (IH) depending on a MZ dose. For equally effective potentiation of the effect of radiation on a tumor during a combined use of MZ and postradiation IH a 4-fold lower dose of the drug was required as combined to MZ used alone. The combined effect of the modifiers was superadditive. The use of IH in this scheme not only potentiated skin radiation reactions on a tumor growth zone but also slighly weakened their expression

Oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

Science.gov (United States)

Aisa, Yoshinobu; Mori, Takehiko; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Yokoyama, Akihiro; Ikeda, Yasuo; Okamoto, Shinichiro

2005-04-01

The purpose of this study was to evaluate the efficacy of oral cryotherapy to prevent high-dose melphalan-induced stomatitis. Eighteen consecutive recipients of allogeneic hematopoietic stem cell transplant conditioned with high-dose melphalan (140 mg/m2) in combination with fludarabine alone or with fludarabine and additional chemotherapy or radiation were enrolled. The severity of stomatitis was graded according to the National Cancer Institute Common Toxicity Criteria. Patients were kept on oral cryotherapy using ice chips and ice-cold water shortly before, during, and for additional 90 min after completion of melphalan administration. Only two of 18 patients (11.1%) developed grade 2 or 3 stomatitis while six of seven patients in the historical control developed it (85.7%; P=0.001). These results suggested that oral cryotherapy could effectively prevent stomatitis caused by high-dose melphalan, and we recommend that it should be incorporated into the conditioning regimen with high-dose melphalan.

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

Energy Technology Data Exchange (ETDEWEB)

Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

2017-01-01

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

Drug–drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer

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Park G

2017-03-01

Full Text Available Gab-jin Park,1 Soo Hyeon Bae,1 Wan-Su Park,1 Seunghoon Han,1 Min-Ho Park,2 Seok-Ho Shin,2 Young G Shin,2 Dong-Seok Yim1,2 1Department of Clinical Pharmacology and Therapeutics, Seoul St Mary’s Hospital, PIPET (Pharmacometrics Institute for Practical Education and Training, College of Medicine, Catholic University of Korea, Seoul, South Korea; 2College of Pharmacy, Chungnam National University, Daejeon, South Korea Purpose: A microdose drug–drug interaction (DDI study may be a valuable tool for anticipating drug interaction at therapeutic doses. This study aimed to compare the magnitude of DDIs at microdoses and regular doses to explore the applicability of a microdose DDI study. Patients and methods: Six healthy male volunteer subjects were enrolled into each DDI study of omeprazole (victim and known perpetrators: fluconazole (inhibitor and rifampin (inducer. For both studies, the microdose (100 µg, cold compound and the regular dose (20 mg of omeprazole were given at days 0 and 1, respectively. On days 2–9, the inhibitor or inducer was given daily, and the microdose and regular dose of omeprazole were repeated at days 8 and 9, respectively. Full omeprazole pharmacokinetic samplings were performed at days 0, 1, 8, and 9 of both studies for noncompartmental analysis. Results: The magnitude of the DDI, the geometric mean ratios (with perpetrator/omeprazole only of maximum concentration (Cmax and area under the curve to the last measurement (AUCt of the microdose and the regular dose were compared. The geometric mean ratios in the inhibition study were: 2.17 (micro and 2.68 (regular for Cmax, and 4.07 (micro, 4.33 (regular for AUCt. For the induction study, they were 0.26 (micro and 0.21 (regular for Cmax, and 0.16 (micro and 0.15 (regular for AUCt. There were no significant statistical differences in the magnitudes of DDIs between microdose and regular-dose conditions, regardless of induction or inhibition. Conclusion: Our results may be

Lumbosacral plexus delineation, dose distribution, and its correlation with radiation-induced lumbosacral plexopathy in cervical cancer patients

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Tunio M

2014-12-01

Full Text Available Mutahir Tunio,1 Mushabbab Al Asiri,1 Yasser Bayoumi,2 Ali Abdullah O Balbaid,1 Majed AlHameed,3 Stanciu Laura Gabriela,1 Ahmad Amir O Ali1 1Radiation Oncology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia; 2National Cancer Institute, Cairo University, Cairo, Egypt; 3Neurology, Comprehensive Cancer Center, King Fahad Medical City, Riyadh, Saudi Arabia Background: To evaluate the dose distribution to the lumbosacral plexus (LSP and its correlation with radiation-induced lumbosacral plexopathy (RILSP in patients with cervical cancer treated with intensity-modulated radiotherapy (IMRT and high-dose-rate brachytherapy.Materials and methods: After meeting eligibility criteria, 50 patients with cervical cancer were selected who were treated with IMRT and high-dose-rate brachytherapy, and the LSP was contoured. Mean volume; percentages of LSP volume absorbing 40, 50, 55, and 60 Gy (V30, V40, V50, V55, and V60 and point doses (P1, P2, P3, P4, P5, P6, P7, P8, P9, and P10; and RILSP incidence were calculated.Results: At 60 months of follow-up, four patients (8% were found to have grade 2/3 RILSP. The mean maximal LSP dose in patients with RILSP was 59.6 Gy compared with 53.9 Gy in patients without RILSP (control; P=0.04. The mean values of V40, V50, V55, and V60 in patients with RILSP versus control were 61.8% versus 52.8%, 44.4% versus 27.7%, 8.0% versus 0.3% and 1.8% versus 0%, respectively (P=0.01, 0.001, 0.001, and 0.001, respectively.Conclusion: The delineation of the LSP during IMRT planning may reduce the risk for RILSP. The mean values of V40, V50, V55, and V60 for LSP should be less than 55%, 30%, 5%, and 0.5%, respectively; however, further studies are warranted.Keywords: cervical cancer, intensity-modulated radiation therapy, lumbosacral plexus delineation, radiation-induced lumbosacral plexopathy, dosimetric analysis

Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different fractionation schedules

International Nuclear Information System (INIS)

Liebmann, A.; Hindemith, M.; Jahns, J.; Kamprad, F.; Hildebrandt, G.; Madaj-Sterba, P.; Weisheit, S.

2004-01-01

Background and purpose: low-dose radiotherapy is widely accepted as a very effective treatment option for inflammatory symptoms associated with painful degenerative joint disorders. Radiation doses and fractionation schedules in practical use are empirical and mainly based on clinical observations. Experimental data are rare. The efficacy of low-dose X-irradiation on adjuvant induced arthritis in rats using different fractionation schemes was investigated in vivo, in order to explore whether there is a dose and fractionation dependence. Material and methods: adjuvant arthritis in female lewis rats (n = 128) was induced by intradermal injection of heat-inactivated Mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham-irradiated (group 1: days 10-14; group 2: days 15-19; group 3: days 22-26) or X-irradiated with either 5 x 1.0 Gy (group 4: days 10-14; group 6: days 15-19; group 8: days 22-26; group 10: days 10, 12, 14, 16, and 18) or 5 x 0.5 Gy (group 5: days 10-14; group 7: days 15-19; group 9: days 22-26; group 11: days 10, 12, 14, 16, and 18; group 12: days 10-14 and 22-26). The clinical parameters arthritis score (AS), hind paw volume (HPV), and body weight were determined. Results: a significant decrease of the clinical arthritis parameters was observed following 5 x 0.5 Gy or 5 x 1.0 Gy during the acute maximum of the inflammatory response (days 15-19). The most pronounced treatment effect was reached after two daily fractionated series of 5 x 0.5 Gy with an early treatment onset (days 10-14) and repetition in interval (days 22-26). After the application of 5 x 1.0 Gy on days 10-14 or in a protracted scheme (days 10, 12, 14, 16, and 18), only a nonsignificant positive trend could be detected. Daily fractionated X-irradiation in the chronic phase of adjuvant arthritis (days 22-26) did not show any positive clinical effect. Conclusion: low-dose radiotherapy is able to prevent a full-blown arthritic reaction if given during the florid phase of

Preventive effects of lansoprazole and famotidine on gastric mucosal injury induced by low-dose aspirin in Helicobacter pylori-negative healthy volunteers.

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Nishino, Masafumi; Sugimoto, Mitsushige; Kodaira, Chise; Yamade, Mihoko; Uotani, Takahiro; Shirai, Naohito; Ikuma, Mutsuhiro; Tanaka, Tatsuo; Sugimura, Haruhiko; Hishida, Akira; Furuta, Takahisa

2011-07-01

The preventive effects of lansoprazole and famotidine on low-dose aspirin-induced gastric mucosal injury in relation to gastric acidity were compared in healthy Japanese volunteers. Fifteen Helicobacter pylori-negative volunteers with different CYP2C19 genotypes were randomly administered aspirin 100 mg, aspirin plus famotidine 20 mg twice daily, or aspirin plus lansoprazole 15 mg once daily for 7 days each in a crossover fashion. Gastroscopy for the evaluation of mucosal injury based on modified Lanza score (MLS) and 24-hour intragastric pH monitoring were performed on day 7 of each regimen. Aspirin induced gastric mucosal injury (median MLS = 3). Lansoprazole significantly decreased MLS to 0, which was significantly lower than that by famotidine (MLS = 1) (P lansoprazole regimen were significantly higher than those with famotidine (P lansoprazole appeared to be more protective than famotidine against low-dose aspirin-induced mucosal injury but a larger well-controlled study is necessary to establish a definitive clinical benefit.

A Systems Genetic Approach to Identify Low Dose Radiation-Induced Lymphoma Susceptibility/DOE2013FinalReport

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Balmain, Allan [University of California, San Francisco; Song, Ihn Young [University of California, San Francisco

2013-05-15

The ultimate goal of this project is to identify the combinations of genetic variants that confer an individual's susceptibility to the effects of low dose (0.1 Gy) gamma-radiation, in particular with regard to tumor development. In contrast to the known effects of high dose radiation in cancer induction, the responses to low dose radiation (defined as 0.1 Gy or less) are much less well understood, and have been proposed to involve a protective anti-tumor effect in some in vivo scientific models. These conflicting results confound attempts to develop predictive models of the risk of exposure to low dose radiation, particularly when combined with the strong effects of inherited genetic variants on both radiation effects and cancer susceptibility. We have used a Systems Genetics approach in mice that combines genetic background analysis with responses to low and high dose radiation, in order to develop insights that will allow us to reconcile these disparate observations. Using this comprehensive approach we have analyzed normal tissue gene expression (in this case the skin and thymus), together with the changes that take place in this gene expression architecture a) in response to low or high- dose radiation and b) during tumor development. Additionally, we have demonstrated that using our expression analysis approach in our genetically heterogeneous/defined radiation-induced tumor mouse models can uniquely identify genes and pathways relevant to human T-ALL, and uncover interactions between common genetic variants of genes which may lead to tumor susceptibility.

Dose-response study of the hematological toxicity induced by vectorized radionuclides in a mouse model

International Nuclear Information System (INIS)

Rousseau-Poivet, J.; Sas, N.; Nguyen, F.; Abadie, J.; Chouin, N.; Barbet, J.

2015-01-01

studied progenitor and blood cells. As compared to 0.8 Gy, one more week was necessary at 1.4 Gy. A mild anemia (21% erythrocyte depletion) was noticed only at this higher absorbed dose between D3 and D10. Conclusion: absorbed doses to the BM between 0.8 and 1.4 Gy induced hematological toxicity expressed by transient BM aplasia, neutropenia, thrombocytopenia and inconsistent anemia. These depletions and time to recovery were both dose-dependent. Higher absorbed doses will be achieved to better investigate the dose-response relationship and to further develop our compartmental model for platelets. Neutrophils and erythrocytes kinetics are also under investigation to generate satisfying simulations with the model. (authors)

Pyrrolizidine alkaloid-derived DNA adducts as a common biological biomarker of pyrrolizidine alkaloid-induced tumorigenicity.

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Xia, Qingsu; Zhao, Yuewei; Von Tungeln, Linda S; Doerge, Daniel R; Lin, Ge; Cai, Lining; Fu, Peter P

2013-09-16

Pyrrolizidine alkaloid-containing plants are the most common poisonous plants affecting livestock, wildlife, and humans. The U.S. National Toxicology Program (NTP) classified riddelliine, a tumorigenic pyrrolizidine alkaloid, as "reasonably anticipated to be a human carcinogen" in the NTP 12th Report on Carcinogens in 2011. We previously determined that four DNA adducts were formed in rats dosed with riddelliine. The structures of the four DNA adducts were elucidated as (i) a pair of epimers of 7-hydroxy-9-(deoxyguanosin-N(2)-yl)dehydrosupinidine adducts (termed as DHP-dG-3 and DHP-dG-4) as the predominant adducts; and (ii) a pair of epimers of 7-hydroxy-9-(deoxyadenosin-N(6)-yl)dehydrosupinidine adducts (termed as DHP-dA-3 and DHP-dA-4 adducts). In this study, we selected a nontumorigenic pyrrolizidine alkaloid, platyphylliine, a pyrrolizidine alkaloid N-oxide, riddelliine N-oxide, and nine tumorigenic pyrrolizidine alkaloids (riddelliine, retrorsine, monocrotaline, lycopsamine, retronecine, lasiocarpine, heliotrine, clivorine, and senkirkine) for study in animals. Seven of the nine tumorigenic pyrrolizidine alkaloids, with the exception of lycopsamine and retronecine, are liver carcinogens. At 8-10 weeks of age, female F344 rats were orally gavaged for 3 consecutive days with 4.5 and 24 μmol/kg body weight test article in 0.5 mL of 10% DMSO in water. Twenty-four hours after the last dose, the rats were sacrificed, livers were removed, and liver DNA was isolated for DNA adduct analysis. DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts were formed in the liver of rats treated with the individual seven hepatocarcinogenic pyrrolizidine alkaloids and riddelliine N-oxide. These DNA adducts were not formed in the liver of rats administered retronecine, the nontumorigenic pyrrolizidine alkaloid, platyphylliine, or vehicle control. These results indicate that this set of DNA adducts, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4, is a common biological biomarker of

Effect of Bcl-2/Bax gene expression on apoptosis of spermatogenic cells of mouse testes induced by low dose radiation

International Nuclear Information System (INIS)

Liu Guangwei; Wang Chunyan; Lu Zhe; Liu Shunchun; Gong Shouliang

2003-01-01

The different kinds of spermatogenic cells were separated using density gradient centrifugation and their apoptosis and Bcl-2 and Bax protein expression were measured with flow cytometry and immunohistochemical method, respectively. The results showed the apoptosis in all kinds of spermatogenic cells induced by low dose radiation (LDR) had a obvious regularity. When the doses were 0.025 and 0.05 Gy, spermatogonia apoptosis was dominant. With the increase of irradiation dose (0.075-0.2 Gy), spermatocytes also showed an apoptotic change, but the apoptotic percentage of spermatogonia was significantly higher than that of spermatocytes. Moreover, the apoptosis of spermatids and spermatozoa scarcely occurred after LDR. Bax protein was primarily expressed in spermatogonia and spermatocytes, and the former was significantly higher than that of the latter after LDR. With the increase of irradiation dose, Bax protein expression showed a upgrading tendency, but that of spermatids and spermatozoa scarcely occurred. Bcl-2 protein was primarily expressed in spermatids and spermatozoa, but the Bcl-2 protein expressions of spermatogonia and spermatocytes scarcely occurred after LDR. These results imply that the interacting regulation of Bcl-2 and Bax gene expression might be involved in selective apoptosis of spermatogenic cells induced by LDR, which provided an experimental evidence for further exploring the apoptotic mechanism of adaptive response of spermatogenic cells by LDR

Suitable gamma ray dose determination in order to induce genetic variation in kaboli chickpea (Cicer Arietinum L)

International Nuclear Information System (INIS)

Naserian Khiabani, B.; Ahari Mostafavi, H.; Fathollahi, H.; Vedadi, S.; Mosavi Shalmani, M. A.

2008-01-01

In spite of chickpea's use in Iran and its ability of being replaced to adjust the shortage of protein in dietary habits, yield production is very low. One of the main reasons for chickpea's low yield production is its sensitiveness to some diseases, pest and environmental stresses. Genetic variation in chickpea is very low, because of its self pollination. In breeding programs, genetic variation plays an essential role so that the induction of genetic variation in plant population is very important for the plant breeders. The induced mutation through different kinds of mutagens is one of the important ways of genetic variation. In this research, first the sensitiveness of four cultivars (ILC.486, Philip86, Bivinich, Jam) were assessed to different gamma ray doses (100, 200, 300, 400 Gy). The results showed that with an increase in gamma ray dose, the growth rate of chickpea's genotypes decreases. In this respect, the decrease of growth rate has a linear relationship with the gamma ray dose and it is independent from the genotypes. The root length is more sensitive to gamma ray doses than its shoot, and it was observed that at the low doses the root growth decreases, comparing to the shoot growth. On the other hand, in high doses of gamma ray growth abrasion (Ageotropism, Albinism and etc.) were observed. Some traits variation (such as leaf shape, leaf size, leaf color, Albinism, etc.) were seen in M 2 generation, and finally to continue the project, three doses of gamma ray (150,200,250) were selected for the next year

Therapeutic doses of doxorubicin induce premature senescence of human mesenchymal stem cells derived from menstrual blood, bone marrow and adipose tissue.

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Kozhukharova, Irina; Zemelko, Victoria; Kovaleva, Zoya; Alekseenko, Larisa; Lyublinskaya, Olga; Nikolsky, Nikolay

2018-03-01

Doxorubicin (Dox) is an effective anticancer drug with known activity against a wide spectrum of malignancies, hematologic malignancies in particular. Despite extensive clinical use, the mechanisms of its side effects and negative action on normal cells remain under study. The aim of this study was to investigate the effect of Dox on cultured human mesenchymal stem cells (MSCs) derived from menstrual blood (eMSCs), bone marrow (BMSCs) and adipose tissue (AMSCs). Dox treatment in high doses decreased the survival of MSCs in a dose-dependent manner. Clinically relevant low doses of Dox induced premature senescence of eMSCs, BMSCs and AMSCs, but did not kill the cells. Dox caused cell cycle arrest and formation of γ-H2AX foci, and increased the number of SA-β-gal-positive cells. BMSCs entered premature senescence earlier than other MSCs. It has been reported that neural-like cells differentiated from MSCs of various origins are more sensitive to Dox than their parent cells. Dox-treated differentiated MSCs exhibited lower viability and earlier generation of γ-H2AX foci. Dox administration inhibited secretory activity in neural-like cells. These findings suggest that a clinically relevant Dox dose damages cultured MSCs, inducing their premature senescence. MSCs are more resistant to this damage than differentiated cells.

Methanolic extract of Moringa oleifera leaf and low doses of gamma radiation alleviated amiodarone-induced lung toxicity in albino rats

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Hasan Hesham F.

2016-01-01

Full Text Available This study aimed to evaluate the effects of methanolic extract of Moringa oleifera (MO and/or low doses of gamma radiation (LDR on amiodarone (AMD-induced lung toxicity in rats. AMD administered to female albino rats (100 mg/kg body weight for 10 consecutive days. Rats received methanolic extract of MO (250 mg/kg bwt for 15 successive days and/or were exposed to whole body LDR (0.25Gy on the 1st and 10th days, up to a total dose of 0.5Gy. MO administration induced a significant decrease in serum tumor necrosis factor-alpha (TNF-α and transforming growth factor-beta (TGF-β levels as well as lactate dehydrogenase (LDH activity. Also, the content of malondialdehyde (MDA and hydroxyproline (HYP was significantly decreased in lung tissue. Furthermore, MO significantly increased reduced glutathione (GSH content in lung tissue as compared with AMD. The histopathological investigation of lung tissue revealed the appearance of interstitial pneumonia in rats treated with AMD. The oral administration of MO and/or exposure to LDR reversed the biochemical and histopathological alterations induced by AMD. It can be posited that MO and LDR might have a considerable role in the prevention of lung toxicity induced by AMD.

Low-dose cyclophosphamide administered as daily or single dose enhances the antitumor effects of a therapeutic HPV vaccine

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Peng, Shiwen; Lyford-Pike, Sofia; Akpeng, Belinda; Wu, Annie; Hung, Chien-Fu; Hannaman, Drew; Saunders, John R.; Wu, T.-C.

2012-01-01

Although therapeutic HPV vaccines are able to elicit systemic HPV-specific immunity, clinical responses have not always correlated with levels of vaccine-induced CD8+ T cells in human clinical trials. This observed discrepancy may be attributable to an immunosuppressive tumor microenvironment in which the CD8+ T cells are recruited. Regulatory T cells (Tregs) are cells that can dampen cytotoxic CD8+ T-cell function. Cyclophosphamide (CTX) is a systemic chemotherapeutic agent, which can eradicate immune cells, including inhibitory Tregs. The optimal dose and schedule of CTX administration in combination with immunotherapy to eliminate the Treg population without adversely affecting vaccine-induced T-cell responses is unknown. Therefore, we investigated various dosing and administration schedules of CTX in combination with a therapeutic HPV vaccine in a preclinical tumor model. HPV tumor-bearing mice received either a single preconditioning dose or a daily dose of CTX in combination with the pNGVL4a-CRT/E7(detox) DNA vaccine. Both single and daily dosing of CTX in combination with vaccine had a synergistic anti-tumor effect as compared to monotherapy alone. The potent antitumor responses were attributed to the reduction in Treg frequency and increased infiltration of HPV16 E7-specific CD8+ T cells, which led to higher ratios of CD8+/Treg and CD8+/CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs). There was an observed trend toward decreased vaccine-induced CD8+ T-cell frequency with daily dosing of CTX. We recommend a single, preconditioning dose of CTX prior to vaccination due to its efficacy, ease of administration, and reduced cumulative adverse effect on vaccine-induced T cells. PMID:23011589

Organ dose and effective dose with the EOS scanner in spine deformity surgery

DEFF Research Database (Denmark)

Heide Pedersen, Peter; Petersen, Asger Greval; Eiskjær, Søren Peter

2016-01-01

Organ dose and effective dose with the EOS scanner in spine deformity surgery. A study on anthropomorphic phantoms describing patient radiation exposure in full spine examinations. Authors: Peter Heide Pedersen, Asger Greval Petersen, Søren Peter Eiskjær. Background: Ionizing radiation potentially...... quality images while at the same time reducing radiation dose. At our institution we use the EOS for pre- and postoperative full spine examinations. Purpose: The purpose of the study is to make first time organ dose and effective dose evaluations with micro-dose settings in full spine examinations. Our...... hypothesis is that organ dose and effective doses can be reduced 5-10 times compared to standard settings, without too high image-quality trade off, resulting in a theoretical reduction of radiation induced cancer. Methods: Patient dosimetry is performed on anthropomorphic child phantoms, representing a 5...

Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

Science.gov (United States)

Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

Comparison of the dose-response relationship of radiation-induced apoptosis in the hippocampal dentate gyrus and intestinal crypt of adult mice

International Nuclear Information System (INIS)

Kim, J. S.; Yang, M.; Kim, J.; Lee, D.; Kim, J. C.; Shin, T.; Kim, S. H.; Moon, C.

2012-01-01

The present study compared the dose-response curves for the frequency of apoptosis in mouse hippocampal dentate gyrus (DG) and intestinal crypt using whole-body gamma irradiation. The incidence of gamma-ray-induced apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labelling (TUNEL) method. TUNEL-positive apoptotic nuclei in the DG and intestinal crypt were increased in a dose-dependent pattern (0-2 Gy). The dose-response curves were linear-quadratic, with a significant relationship between the appearance of apoptosis and irradiation dose. The slopes of the dose-response curves in the DG were much steeper (∼5-6-fold) than those in the intestinal crypt within the range of 0-1 Gy exposure. Hippocampal DG might be a more effective and sensitive evaluation structure than the intestinal crypt to estimate the degree of radiation exposure in damaged organs of adult mice exposed to low irradiation dose. copy; The Author 2011. Published by Oxford Univ. Press. All rights reserved. (authors)

Low-dose computed tomography image restoration using previous normal-dose scan

International Nuclear Information System (INIS)

Ma, Jianhua; Huang, Jing; Feng, Qianjin; Zhang, Hua; Lu, Hongbing; Liang, Zhengrong; Chen, Wufan

2011-01-01

Purpose: In current computed tomography (CT) examinations, the associated x-ray radiation dose is of a significant concern to patients and operators. A simple and cost-effective means to perform the examinations is to lower the milliampere-seconds (mAs) or kVp parameter (or delivering less x-ray energy to the body) as low as reasonably achievable in data acquisition. However, lowering the mAs parameter will unavoidably increase data noise and the noise would propagate into the CT image if no adequate noise control is applied during image reconstruction. Since a normal-dose high diagnostic CT image scanned previously may be available in some clinical applications, such as CT perfusion imaging and CT angiography (CTA), this paper presents an innovative way to utilize the normal-dose scan as a priori information to induce signal restoration of the current low-dose CT image series. Methods: Unlike conventional local operations on neighboring image voxels, nonlocal means (NLM) algorithm utilizes the redundancy of information across the whole image. This paper adapts the NLM to utilize the redundancy of information in the previous normal-dose scan and further exploits ways to optimize the nonlocal weights for low-dose image restoration in the NLM framework. The resulting algorithm is called the previous normal-dose scan induced nonlocal means (ndiNLM). Because of the optimized nature of nonlocal weights calculation, the ndiNLM algorithm does not depend heavily on image registration between the current low-dose and the previous normal-dose CT scans. Furthermore, the smoothing parameter involved in the ndiNLM algorithm can be adaptively estimated based on the image noise relationship between the current low-dose and the previous normal-dose scanning protocols. Results: Qualitative and quantitative evaluations were carried out on a physical phantom as well as clinical abdominal and brain perfusion CT scans in terms of accuracy and resolution properties. The gain by the use

Evaluation of the Effect of Different Doses of Low Energy Shock Wave Therapy on the Erectile Function of Streptozotocin (STZ-Induced Diabetic Rats

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Zhong-Cheng Xin

2013-05-01

Full Text Available To investigate the therapeutic effect of different doses of low energy shock wave therapy (LESWT on the erectile dysfunction (ED in streptozotocin (STZ induced diabetic rats. SD rats (n = 75 were randomly divided into 5 groups (normal control, diabetic control, 3 different dose LESWT treated diabetic groups. Diabetic rats were induced by intra-peritoneal injection of STZ (60 mg/kg and rats with fasting blood glucose ≥ 300 mg/dL were selected as diabetic models. Twelve weeks later, different doses of LESWT (100, 200 and 300 shocks each time treatment on penises were used to treat ED (7.33 MPa, 2 shocks/s three times a week for two weeks. The erectile function was evaluated by intracavernous pressure (ICP after 1 week washout period. Then the penises were harvested for histological study. The results showed LESWT could significantly improve the erectile function of diabetic rats, increase smooth muscle and endothelial contents, up-regulate the expression of α-SMA, vWF, nNOS and VEGF, and down- regulate the expression of RAGE in corpus cavernosum. The therapeutic effect might relate to treatment dose positively, and the maximal therapeutic effect was noted in the LESWT300 group. Consequently, 300 shocks each time might be the ideal LESWT dose for diabetic ED treatment.

Phenobarbital Induces Alterations in the Proteome of Hepatocytes and Mesenchymal Cells of Rat Livers

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Klepeisz, Philip; Sagmeister, Sandra; Haudek-Prinz, Verena; Pichlbauer, Melanie; Grasl-Kraupp, Bettina; Gerner, Christopher

2013-01-01

Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs) have concentrated on alterations induced in hepatocytes (HCs). A potential role of non-parenchymal liver cells (NPCs) in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB) which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme. PMID:24204595

Phenobarbital induces alterations in the proteome of hepatocytes and mesenchymal cells of rat livers.

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Philip Klepeisz

Full Text Available Preceding studies on the mode of action of non-genotoxic hepatocarcinogens (NGCs have concentrated on alterations induced in hepatocytes (HCs. A potential role of non-parenchymal liver cells (NPCs in NGC-driven hepatocarcinogenesis has been largely neglected so far. The aim of this study is to characterize NGC-induced alterations in the proteome profiles of HCs as well as NPCs. We chose the prototypic NGC phenobarbital (PB which was applied to male rats for a period of 14 days. The livers of PB-treated rats were perfused by collagenase and the cell suspensions obtained were subjected to density gradient centrifugation to separate HCs from NPCs. In addition, HCs and NPC isolated from untreated animals were treated with PB in vitro. Proteome profiling was done by CHIP-HPLC and ion trap mass spectrometry. Proteome analyses of the in vivo experiments showed many of the PB effects previously described in HCs by other methods, e.g. induction of phase I and phase II drug metabolising enzymes. In NPCs proteins related to inflammation and immune regulation such as PAI-1 and S100-A10, ADP-ribosyl cyclase 1 and to cell migration such as kinesin-1 heavy chain, myosin regulatory light chain RLC-A and dihydropyrimidinase-related protein 1 were found to be induced, indicating major PB effects on these cells. Remarkably, in vitro treatment of HCs and NPCs with PB hardly reproduced the proteome alterations observed in vivo, indicating differences of NGC induced responses of cells at culture conditions compared to the intact organism. To conclude, the present study clearly demonstrated that PB induces proteome alterations not only in HCs but also in NPCs. Thus, any profound molecular understanding on the mode of action of NGCs has to consider effects on cells of the hepatic mesenchyme.

Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation

International Nuclear Information System (INIS)

Han Wei; Zhu Lingyan; Jiang Erkang; Wang Jun; Chen Shaopeng; Bao Linzhi; Zhao Ye; Xu An; Yu Zengliang; Wu Lijun

2007-01-01

Previous studies have shown that high NaCl can be genotoxic, either alone or combined with irradiation. However, little is known about the relationship between environmental NaCl at elevated conditions and radiation-induced bystander effects (RIBE). RIBE, which has been considered as non-targeted bystander responses, has been demonstrated to occur widely in various cell lines. In the present study, RIBE under the elevated NaCl culture condition was assessed in AG 1522 cells by both the induction of γ-H2AX, a reliable marker of DNA double-strand break (DSB) for the early process ( G -methyl-L-arginine, an inhibitor of nitric oxide synthase, the induced fraction of foci-positive cells was effectively inhibited both in 0.2 cGy α-particle irradiated and adjacent non-irradiated regions under either normal or elevated NaCl conditions. These results suggested that the cultures with elevated NaCl medium magnified the damage effects induced by the low dose α-particle irradiation and nitric oxide generated by irradiation was also very important in this process

Biological radiation dose estimation by chromosomal aberrations analysis in human peripheral blood (dose-effect curve)

International Nuclear Information System (INIS)

Al-Achkar, W.

2001-09-01

In order to draw a dose-effect curve, experimentally gamma ray induced chromosomal aberrations in human peripheral lymphocytes from eight healthy people were studied. Samples from 4 males and 4 females were irradiated in tubes with 0.15, 0.25, 0.5, 1, 1.5, 2, 2.5 gray of gamma ray (Co 60 at dose rate 0.3 Gy/min). Irradiated and control samples were incubated in 37 centigrade for 48 hours cell cultures. Cell cultures then were stopped and metaphases spread, Giemsa stained to score the induced chromosomal aberrations. Chromosomal aberrations from 67888 metaphases were scored. Curves from the total number of dicentrics, dicentrics + rings and total numbers of breaks in cell for each individual or for all people were drawn. An increase of all chromosomal aberrations types with the elevation of the doses was observed. The yield of chromosome aberrations is related to the dose used. These curves give a quick useful estimation of the accidentally radiation exposure. (author)

Radiation-induced changes in breathing frequency and lung histology of C57BL/6J mice are time- and dose-dependent

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Eldh, T.; Heinzelmann, F.; Velalakan, A. [Univ. Hospital of Tuebingen (Germany). Dept. of Radiation Oncology; Budach, W. [Duesseldorf Univ. (Germany). Dept. of Radiation Oncology; Belka, C. [Univ. Hospital of Tuebingen (Germany). Dept. of Radiation Oncology; Muenchen Univ. (Germany). Dept. of Radiation Oncology; Jendrossek, V. [Univ. Hospital of Tuebingen (Germany). Dept. of Radiation Oncology; Duisburg-Essen Univ., Essen (DE). Inst. of Cell Biology (Cancer Research)

2012-03-15

Pneumonitis and fibrosis constitute serious adverse effects of radiotherapy in the thoracic region. In this study, time-course and dose-dependence of clinically relevant parameters of radiation-induced lung injury in C57BL/6J mice were analyzed. A well-characterized disease model is necessary for the analysis of the cellular and molecular mechanisms using genetically modified mice. C57BL/6J mice received single dose right hemithorax irradiation with 12.5 or 22.5 Gy. Body weight and breathing frequency were recorded as parameters for health impairment. Lung tissue was collected over 24 weeks for histological analysis. Hemithorax irradiation with 12.5 or 22.5 Gy induced biphasic breathing impairment with the first increase between days 7 and 70. Although breathing impairment was more pronounced in the 22.5 Gy group, it was accompanied in both dose groups by pneumonitis-associated histological changes. A second rise in breathing frequency ratios became visible starting on day 70 with a steady increase until day 210. Again, breathing was more strongly affected in the 22.5 Gy group. However, breathing impairment coincided only in the 22.5 Gy group with a significant increase in collagen deposition in the lung tissue by day 210. Tissue inflammation and fibrosis were observed in the irradiated and the shielded lungs, pointing toward involvement of systemic effects. Hemithorax irradiation induces time-dependent pneumonitis and fibrosis in C57BL/6J mice. While hemithorax irradiation with 12.5 Gy is sufficient to induce lung inflammation, it is below the threshold for collagen deposition and fibrosis development by day 210.

High-dose irradiation induces cell cycle arrest, apoptosis, and developmental defects during Drosophila oogenesis.

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Hee Jin Shim

Full Text Available Ionizing radiation (IR treatment induces a DNA damage response, including cell cycle arrest, DNA repair, and apoptosis in metazoan somatic cells. Because little has been reported in germline cells, we performed a temporal analysis of the DNA damage response utilizing Drosophila oogenesis as a model system. Oogenesis in the adult Drosophila female begins with the generation of 16-cell cyst by four mitotic divisions of a cystoblast derived from the germline stem cells. We found that high-dose irradiation induced S and G2 arrests in these mitotically dividing germline cells in a grp/Chk1- and mnk/Chk2-dependent manner. However, the upstream kinase mei-41, Drosophila ATR ortholog, was required for the S-phase checkpoint but not for the G2 arrest. As in somatic cells, mnk/Chk2 and dp53 were required for the major cell death observed in early oogenesis when oocyte selection and meiotic recombination occurs. Similar to the unscheduled DNA double-strand breaks (DSBs generated from defective repair during meiotic recombination, IR-induced DSBs produced developmental defects affecting the spherical morphology of meiotic chromosomes and dorsal-ventral patterning. Moreover, various morphological abnormalities in the ovary were detected after irradiation. Most of the IR-induced defects observed in oogenesis were reversible and were restored between 24 and 96 h after irradiation. These defects in oogenesis severely reduced daily egg production and the hatch rate of the embryos of irradiated female. In summary, irradiated germline cells induced DSBs, cell cycle arrest, apoptosis, and developmental defects resulting in reduction of egg production and defective embryogenesis.

Blood pressure reduction induced by low dose of epinephrine via different routes in rats.

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Wu, Jing; Ji, Mu-Huo; Wang, Zhong-Yun; Zhu, Wei; Yang, Jian-Jun; Peng, Yong G

2013-09-01

Epinephrine was recently shown to induce a hypotension episode. Activation of β₂-adrenoceptors with smooth muscle relaxation may be the underlying mechanism. This study investigated the effects of ICI 118551, a β₂-adrenoceptors antagonist, on epinephrine-induced blood pressure reduction via different administration routes in rats. A total of 144 Sprague Dawley rats were equally randomized into 3 groups (intranasal, intravenous, and intra-arterial administration), each with 4 subgroups: saline + saline, ICI 118551 + saline, saline + epinephrine, and ICI 118551 + epinephrine. All rats were anesthetized while spontaneously breathing. Epinephrine was administered at doses of 5 μg/kg via nose, 0.25 μg/kg via femoral vein, and 0.1 μg/kg via aorta. Mean arterial pressure and heart rate were monitored. Mean arterial pressure decreased in all 3 saline + epinephrine subgroups after administration (P blood pressure reduction can be prevented by ICI 118551 in rats, suggesting that the activation of β₂-adrenoceptors contributes to blood pressure reduction.

Radiation dose rate affects the radiosensitization of MCF-7 and HeLa cell lines to X-rays induced by dextran-coated iron oxide nanoparticles.

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Khoshgard, Karim; Kiani, Parvaneh; Haghparast, Abbas; Hosseinzadeh, Leila; Eivazi, Mohammad Taghi

2017-08-01

The aim of radiotherapy is to deliver lethal damage to cancerous tissue while preserving adjacent normal tissues. Radiation absorbed dose of the tumoral cells can increase when high atomic nanoparticles are present in them during irradiation. Also, the dose rate is an important aspect in radiation effects that determines the biological results of a given dose. This in vitro study investigated the dose-rate effect on the induced radiosensitivity by dextran-coated iron oxide in cancer cells. HeLa and MCF-7 cells were cultured in vitro and incubated with different concentrations of dextran-coated iron oxide nanoparticles. They were then irradiated with 6 MV photons at dose rates of 43, 185 and 370 cGy/min. The MTT test was used to obtain the cells' survival after 48 h of irradiations. Incubating the cells with the nanoparticles at concentrations of 10, 40 and 80 μg/ml showed no significant cytotoxicity effect. Dextran-coated iron oxide nanoparticles showed more radiosensitivity effect by increasing the dose rate and nanoparticles concentration. Radiosensitization enhancement factors of MCF-7 and HeLa cells at a dose-rate of 370 cGy/min and nanoparticles' concentration of 80 μg/ml were 1.21 ± 0.06 and 1.19 ± 0.04, respectively. Increasing the dose rate of 6 MV photons irradiation in MCF-7 and HeLa cells increases the radiosensitization induced by the dextran-coated iron nanoparticles in these cells.

[Comparative study on the tolerance and efficacy of high doses of metoclopramide and clebopride in vomiting induced by cisplatin].

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Martín, M; Díaz-Rubio, E

1989-06-10

Forty-one patients treated with cisplatin (100-120 mg/m2), alone or associated with vindesine (3 mg/m2), were included in a randomized crossover pilot study which compared 3 different doses of intravenous clebopride with intravenous metoclopramide. The patients were randomly assigned to receive clebopride in the first chemotherapy course in one of the three dose levels used (0.5 mg/kg, 21 patients; 0.75 mg/kg, 11 patients; 1 mg/kg, 10 patients) or metoclopramide (10 mg/kg). In the second course of the same chemotherapy the patients received the alternative antiemetic, and thus each patient was his own control. The total dose of both antiemetic drugs was infused in 5 intravenous fractions given every 2 hours. The antiemetic activity of clebopride was moderately lower to that of metoclopramide with the first two tested doses (overall doses of 0.5 and 0.75 mg/kg) and similar with the last dose (1 mg/kg). Clebopride was reasonably well tolerated at the used dosages, inducing sedation in 20% of cases (versus 24% with metoclopramide) and diarrhea in 37% (versus 20% with metoclopramide). Extrapyramidal reactions developed in 17% of the courses which included metoclopramide and in none including clebopride. This difference was statistically significant.

Effect of different doses of oxytocin on cardiac electrophysiology and arrhythmias induced by ischemia.

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Houshmand, Fariba; Faghihi, Mahdieh; Imani, Alireza; Kheiri, Soleiman

2017-01-01

The onset of acute myocardial ischemia (MI) is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. This study investigated that whether oxytocin (OT) can modulate ischemia-induced arrhythmias and considered relationships between the severity of arrhythmia and the electrocardiogram parameters during ischemia. OT (0.0001-1 μg) was administrated intraperitoneally 30 min before ischemia. To examine receptor involved, a selective OT-receptor antagonist, atosiban (ATO), was infused 10 min before OT. OT caused a significant and biphasic dose-dependent reduction in ectopic heart activity and arrhythmia score. OT doses that reduced ventricular arrhythmia elicited significant increase in QT interval. OT attenuated the electrophysiological changes associated with MI and there was significant direct relationship between QRS duration and arrhythmia score. ATO treatment reduced beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter OT effects on premature ventricular contractions. We assume that the ability of OT to modulate the electrical activity of the heart may play an important role in the antiarrhythmic actions of OT.

Effect of different doses of oxytocin on cardiac electrophysiology and arrhythmias induced by ischemia

Directory of Open Access Journals (Sweden)

Fariba Houshmand

2017-01-01

Full Text Available The onset of acute myocardial ischemia (MI is accompanied by a rapid increase in electrical instability and often fatal ventricular arrhythmias. This study investigated that whether oxytocin (OT can modulate ischemia-induced arrhythmias and considered relationships between the severity of arrhythmia and the electrocardiogram parameters during ischemia. OT (0.0001–1 μg was administrated intraperitoneally 30 min before ischemia. To examine receptor involved, a selective OT-receptor antagonist, atosiban (ATO, was infused 10 min before OT. OT caused a significant and biphasic dose-dependent reduction in ectopic heart activity and arrhythmia score. OT doses that reduced ventricular arrhythmia elicited significant increase in QT interval. OT attenuated the electrophysiological changes associated with MI and there was significant direct relationship between QRS duration and arrhythmia score. ATO treatment reduced beneficial effects of OT on arrhythmogenesis. Nevertheless, ATO failed to alter OT effects on premature ventricular contractions. We assume that the ability of OT to modulate the electrical activity of the heart may play an important role in the antiarrhythmic actions of OT.

Dose-rate effects for apoptosis and micronucleus formation in gamma-irradiated human lymphocytes

International Nuclear Information System (INIS)

Boreham, D.R.; Dolling, J.-A.; Maves, S.R.; Siwarungsun, N.; Mitchel, R.E.J.

2000-01-01

We have compared dose-rate effects for γ-radiation-induced apoptosis and micronucleus formation in human lymphocytes. Long-term assessment of individual radiation-induced apoptosis showed little intraindividual variation but significant interindividual variation. The effectiveness of radiation exposure to cause apoptosis or micronucleus formation was reduced by low-dose-rate exposures, but the reduction was apparent at different dose rates for these two end points. Micronucleus formation showed a dose-rate effect when the dose rate was lowered to 0.29 cGy/min, but there was no accompanying cell cycle delay. A further increase in the dose-rate effect was seen at 0.15 cGy/min, but was now accompanied by cell cycle delay. There was no dose-rate effect for the induction of apoptosis until the dose rate was reduced to 0.15 cGy/min, indicating that the mechanisms or signals for processing radiation-induced lesions for these two end points must be different at least in part. There appear to be two mechanisms that contribute to the dose-rate effect for micronucleus formation. One of these does not affect binucleate cell frequency and occurs at dose rates higher than that required to produce a dose-rate effect for apoptosis, and one affects binucleate cell frequency, induced only at the very low dose rate which coincidentally produces a dose-rate effect for apoptosis. Since the dose rate at which cells showed reduced apoptosis as well as a further reduction in micronucleus formation was very low, we conclude that the processing of the radiation-induced lesions that induce apoptosis, and some micronuclei, is very slow in quiescent and PHA-stimulated lymphocytes, respectively. (author)

Dose-rate effects for apoptosis and micronucleus formation in gamma-irradiated human lymphocytes

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Boreham, D.R.; Dolling, J.-A.; Maves, S.R. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada); Siwarungsun, N. [Chulalongkorn Univ., Bangkok (Thailand); Mitchel, R.E.J. [Atomic Energy of Canada Limited, Chalk River, Ontario (Canada)

2000-07-01

We have compared dose-rate effects for {gamma}-radiation-induced apoptosis and micronucleus formation in human lymphocytes. Long-term assessment of individual radiation-induced apoptosis showed little intraindividual variation but significant interindividual variation. The effectiveness of radiation exposure to cause apoptosis or micronucleus formation was reduced by low-dose-rate exposures, but the reduction was apparent at different dose rates for these two end points. Micronucleus formation showed a dose-rate effect when the dose rate was lowered to 0.29 cGy/min, but there was no accompanying cell cycle delay. A further increase in the dose-rate effect was seen at 0.15 cGy/min, but was now accompanied by cell cycle delay. There was no dose-rate effect for the induction of apoptosis until the dose rate was reduced to 0.15 cGy/min, indicating that the mechanisms or signals for processing radiation-induced lesions for these two end points must be different at least in part. There appear to be two mechanisms that contribute to the dose-rate effect for micronucleus formation. One of these does not affect binucleate cell frequency and occurs at dose rates higher than that required to produce a dose-rate effect for apoptosis, and one affects binucleate cell frequency, induced only at the very low dose rate which coincidentally produces a dose-rate effect for apoptosis. Since the dose rate at which cells showed reduced apoptosis as well as a further reduction in micronucleus formation was very low, we conclude that the processing of the radiation-induced lesions that induce apoptosis, and some micronuclei, is very slow in quiescent and PHA-stimulated lymphocytes, respectively. (author)

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

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Feinendegen, L.E

2003-07-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach

International Nuclear Information System (INIS)

Feinendegen, L.E.

2003-01-01

In reviewing tissue effects of low-dose radiation (1) absorbed dose to tissue is replaced by the sum of energy deposited with track events in cell-equivalent tissue micromasses, i.e. with microdose hits, in the number of exposed micromasses and (2) induced cell damage and adaptive protection are related to microdose hits in exposed micromasses for a given radiation quality. DNA damage increases with the number of microdose hits. They also can induce adaptive protection, mainly against endogenous DNA damage. This protection involves cellular defenses, DNA repair and damage removal. With increasing numbers of low linear energy transfer (LET) microdose hits in exposed micromasses, adaptive protection first tends to outweigh damage and then (above 200 mGy) fails and largely disappears. These experimental data predict that cancer risk coefficients derived by epidemiology at high-dose irradiation decline at low doses and dose rates when adaptive protection outdoes DNA damage. The dose-risk function should include both linear and non-linear terms at low doses. (author)

Hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose adefovir dipivoxil: a case report and literature review suggesting ethnic predisposition.

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Wu, C; Zhang, H; Qian, Y; Wang, L; Gu, X; Dai, Z

2013-08-01

Adefovir dipivoxil (ADV) is one of the commonly used antiviral agents in the treatment of chronic hepatitis B (CHB) infection. Safety of a daily dose of 10 mg ADV is advocated by the registration trials. We report a case of severe hypophosphatemic osteomalacia and renal Fanconi syndrome induced by low-dose ADV in a CHB-related cirrhosis patient, and discuss the case through a thorough review of other cases reported in the literature. A 48-yr-old Chinese man with CHB-related cirrhosis developed severe progressive generalized bone pain and muscle weakness after receiving ADV 10 mg daily for 54 months. The laboratory results showed severe hypophosphatemia and features of proximal renal tubule dysfunction. Imaging studies were consistent with osteomalacia. After discontinuation of ADV, his symptoms resolved, laboratory abnormalities normalized and imaging studies showed improvement. In addition to our case, 12 other patients have been reported to have developed hypophosphatemic osteomalacia induced by low-dose ADV. Most of the reported cases were of subjects of East-Asian ethnicity. After discontinuation or reduction of ADV, serum phosphate level increased and clinical symptoms significantly improved in all cases. Hypophosphatemic osteomalacia and renal Fanconi syndrome can be associated with low-dose ADV. Clinicians treating CHB patients with ADV 10 mg daily over long periods of time should be aware of this infrequent but serious complication. © 2013 John Wiley & Sons Ltd.

Program for rapid dose assessment in criticality accident, RADAPAS

International Nuclear Information System (INIS)

Takahashi, Fumiaki

2006-09-01

In a criticality accident, a person near fissile material can receive extremely high dose which can cause acute health effect. For such a case, medical treatment should be carried out for the exposed person, according to severity of the exposure. Then, radiation dose should be rapidly assessed soon after an outbreak of an accident. Dose assessment based upon the quantity of induced 24 Na in human body through neutron exposure is expected as one of useful dosimetry techniques in a criticality accident. A dose assessment program, called RADAPAS (RApid Dose Assessment Program from Activated Sodium in Criticality Accidents), was therefore developed to assess rapidly radiation dose to exposed persons from activity of induced 24 Na. RADAPAS consists of two parts; one is a database part and the other is a part for execution of dose calculation. The database contains data compendiums of energy spectra and dose conversion coefficients from specific activity of 24 Na induced in human body, which had been derived in a previous analysis using Monte Carlo calculation code. Information for criticality configuration or characteristics of radiation in the accident field is to be interactively given with interface displays in the dose calculation. RADAPAS can rapidly derive radiation dose to the exposed person from the given information and measured 24 Na specific activity by using the conversion coefficient in database. This report describes data for dose conversions and dose calculation in RADAPAS and explains how to use the program. (author)

Fiber optics in high dose radiation fields

International Nuclear Information System (INIS)

Partin, J.K.

1985-01-01

A review of the behavior of state-of-the-art optical fiber waveguides in high dose (greater than or equal to 10 5 rad), steady state radiation fields is presented. The influence on radiation-induced transmission loss due to experimental parameters such as dose rate, total dose, irradiation history, temperature, wavelength, and light intensity, for future work in high dose environments are given

Dose dependent activation of retinoic acid-inducible gene-I promotes both proliferation and apoptosis signals in human head and neck squamous cell carcinoma.

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Jingzhou Hu

Full Text Available The retinoic-acid-inducible gene (RIG-like receptor (RLR family proteins are major pathogen reorganization receptors (PRR responsible for detection of viral RNA, which initiates antiviral response. Here, we evaluated the functional role of one RLR family member, RIG-I, in human head and neck squamous cell carcinoma (HNSCC. RIG-I is abundantly expressed both in poorly-differentiated primary cancer and lymph node metastasis, but not in normal adjacent tissues. Activation of RIG-I by transfection with low dose of 5'-triphosphate RNA (3p-RNA induces low levels of interferon and proinflammatory cytokines and promotes NF-κB- and Akt-dependent cell proliferation, migration and invasion. In contrast, activation of RIG-I by a high dose of 3p-RNA induces robust mitochondria-derived apoptosis accompanied by decreased activation of Akt, which is independent of the interferon and TNFα receptor, but can be rescued by over-expression of constitutively active Akt. Furthermore, co-immunoprecipitation experiments indicate that the CARD domain of RIG-I is essential for inducing apoptosis by interacting with caspase-9. Together, our results reveal a dual role of RIG-I in HNSCC through regulating activation of Akt, in which RIG-I activation by low-dose viral dsRNA increases host cell survival, whereas higher level of RIG-I activation leads to apoptosis. These findings highlight the therapeutic potential of dsRNA mediated RIG-I activation in the treatment of HNSCC.

Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: Potential implications for neurodegenerative diseases

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Larissa Takser

Full Text Available Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and neuroblastoma N2a cell lines. We tested cylindrospermopsin (CYN, microcystin-LR (MC-LR, and anatoxin-a (ATX-a, individually as well as their mixture. In addition, we studied the neurotoxins β-N-methylamino-l-alanine (BMAA and its isomer 2,4-diaminobutyric acid (DAB, as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of caspases 3/7. Cell death and inflammation are the hallmarks of neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3–15 times more potent at inducing apoptosis and inflammation. Our results suggest that common cyanotoxins at low doses have a potential to induce inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food. Keywords: Cyanotoxins, Low doses, Apoptosis, Inflammation, Brain cells, Neurodegenerative diseases

Influence of contrast agent dose and ultrasound exposure on cardiomyocyte injury induced by myocardial contrast echocardiography in rats.

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Miller, Douglas L; Li, Peng; Dou, Chunyan; Gordon, David; Edwards, Chris A; Armstrong, William F

2005-10-01

To detect specific cardiomyocyte injury induced by myocardial contrast material-enhanced echocardiography (ie, myocardial contrast echocardiography) in rats and to ascertain the influences of contrast material dose and ultrasound exposure on this injury. All animal procedures were approved by the university committee for the use and care of animals. Myocardial contrast echocardiography with 1:4 electrocardiographic (ECG) triggering was performed at 1.5 MHz in 61 anesthetized rats. Evans blue (EB) dye was injected as the vital stain for cardiomyocyte injury. At the start of myocardial contrast echocardiography, which lasted 10 minutes, perflutren lipid microsphere-based contrast material was infused through the tail vein for 5 minutes. Premature heartbeats were counted from the ECG record. The numbers of EB-stained cells counted on sections of heart specimens obtained 24 hours after myocardial contrast echocardiography and then either fresh frozen or embedded in paraffin were determined by using fluorescence microscopy. Results were compared statistically by using t tests and Mann-Whitney rank sum tests. EB-stained cells were concentrated in the anterior region of the myocardium. In the paraffin-embedded specimens, EB-stained cells were often accompanied by but largely separate from areas of inflammatory cell infiltration. At end-systolic triggering with a 50 microL/kg dose of microsphere contrast material, the EB-stained cell count increased with increasing peak rarefactional pressure amplitude, with significantly increased cell counts at 1.6 MPa (P .1). EB-stained cell counts increased with increasing contrast material dose, from 10 to 50 microL/kg, at 2.0 MPa. Cardiomyocyte injury was induced by the interaction of ultrasound pulses with contrast agent microbubbles during myocardial contrast echocardiography in rats, and the numbers of injured cells increased with increasing contrast agent dose and ultrasound exposure. RSNA, 2005

Chromosomal Aberrations in Normal and AT Cells Exposed to High Dose of Low Dose Rate Irradiation

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Kawata, T.; Shigematsu, N.; Kawaguchi, O.; Liu, C.; Furusawa, Y.; Hirayama, R.; George, K.; Cucinotta, F.

2011-01-01

Ataxia telangiectasia (A-T) is a human autosomally recessive syndrome characterized by cerebellar ataxia, telangiectases, immune dysfunction, and genomic instability, and high rate of cancer incidence. A-T cell lines are abnormally sensitive to agents that induce DNA double strand breaks, including ionizing radiation. The diverse clinical features in individuals affected by A-T and the complex cellular phenotypes are all linked to the functional inactivation of a single gene (AT mutated). It is well known that cells deficient in ATM show increased yields of both simple and complex chromosomal aberrations after high-dose-rate irradiation, but, less is known on how cells respond to low-dose-rate irradiation. It has been shown that AT cells contain a large number of unrejoined breaks after both low-dose-rate irradiation and high-dose-rate irradiation, however sensitivity for chromosomal aberrations at low-dose-rate are less often studied. To study how AT cells respond to low-dose-rate irradiation, we exposed confluent normal and AT fibroblast cells to up to 3 Gy of gamma-irradiation at a dose rate of 0.5 Gy/day and analyzed chromosomal aberrations in G0 using fusion PCC (Premature Chromosomal Condensation) technique. Giemsa staining showed that 1 Gy induces around 0.36 unrejoined fragments per cell in normal cells and around 1.35 fragments in AT cells, whereas 3Gy induces around 0.65 fragments in normal cells and around 3.3 fragments in AT cells. This result indicates that AT cells can rejoin breaks less effectively in G0 phase of the cell cycle? compared to normal cells. We also analyzed chromosomal exchanges in normal and AT cells after exposure to 3 Gy of low-dose-rate rays using a combination of G0 PCC and FISH techniques. Misrejoining was detected in the AT cells only? When cells irradiated with 3 Gy were subcultured and G2 chromosomal aberrations were analyzed using calyculin-A induced PCC technique, the yield of unrejoined breaks decreased in both normal and AT

Biological effects of low-dose ionizing radiation exposure

International Nuclear Information System (INIS)

Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst

2009-01-01

The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

The impact of assumptions regarding vaccine-induced immunity on the public health and cost-effectiveness of hepatitis A vaccination: Is one dose sufficient?

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Curran, Desmond; de Ridder, Marc; Van Effelterre, Thierry

2016-01-01

ABSTRACT Hepatitis A vaccination stimulates memory cells to produce an anamnestic response. In this study, we used a mathematical model to examine how long-term immune memory might convey additional protection against clinical/icteric infections. Dynamic and decision models were used to estimate the expected number of cases, and the costs and quality-adjusted life-years (QALYs), respectively. Several scenarios were explored by assuming: (1) varying duration of vaccine-induced immune memory, (2) and/or varying levels of vaccine-induced immune memory protection (IMP), (3) and/or varying levels of infectiousness in vaccinated individuals with IMP. The base case analysis assumed a time horizon of 25 y (2012 – 2036), with additional analyses over 50 and 75 y. The analyses were conducted in the Mexican public health system perspective. In the base case that assumed no vaccine-induced IMP, the 2-dose hepatitis A vaccination strategy was cost-effective compared with the 1-dose strategy over the 3 time horizons. However, it was not cost-effective if we assumed additional IMP durations of at least 10 y in the 25-y horizon. In the 50- and 75-y horizons, the 2-dose strategy was always cost-effective, except when 100% reduction in the probability of icteric Infections, 75% reduction in infectiousness, and mean durations of IMP of at least 50 y were assumed. This analysis indicates that routine vaccination of toddlers against hepatitis A virus would be cost-effective in Mexico using a single-dose vaccination strategy. However, the cost-effectiveness of a second dose depends on the assumptions of additional protection by IMP and the time horizon over which the analysis is performed. PMID:27428611

Predicting radiation effects on the development of leukemic stem cells based on studies of leukemias induced by high- and low-dose-rate radiation

International Nuclear Information System (INIS)

Hirouchi, Tokuhisa

2012-01-01

One of the most important causes of radiation-induced cancers, particularly leukemia, is gene mutations resulting from single and double strand breaks in the DNA. Tanaka et al. (2003) reported life shortening in specific pathogen free male and female B6C3F1 mice continuously exposed to γ rays at a low dose rate of 20 mGy/22 h/d for 400 days from 8 weeks of age. Early death due to cancer, mostly malignant lymphomas, was observed in both sexes. A significant increase in the incidence of myeloid leukemia, resulting in early death, was also reported in males. It is expected however, that at 20 mGy/22 h/d, which is equivalent to a dose of 15 μGy/min, DNA strand breaks induced in these cells are repaired soon after they occur. Murine leukemias induced by high-dose-rate radiation were also found in males, and 80% of the mice with leukemia had hemizygous deletions in chromosome 2 around the PU.1 gene and they appeared to be derived from DNA strand breaks. Majority of these leukemia showing hemizygous deletions in chromosome 2 revealed point mutations in the remaining alleles resulting in PU.1 inactivation, which was reported to be related to leukemogenesis. These point mutations are assumed to be independent of DNA strand breaks that occur immediately after irradiation, as they appear at later time after irradiation. This review discusses the effect of radiation-induced DNA strand breaks and also mutagenesis induced independently of DNA strand breaks in hematopoietic cells contributing to the development of the first leukemic stem cell. (author)

New way of dosing sugammadex for termination of vecuronium induced neuromuscular block

Directory of Open Access Journals (Sweden)

Blaž Peček

2015-06-01

Full Text Available Background and Goal of Study: Sugammadex is a selective binding agent that bindsaminosteroid muscle relaxants. Each molecule of sugammadex binds one molecule of musclerelaxant. To produce the same depth of the neuromuscular block (NMB much less molecules ofvecuronium are needed than molecules of rocuronium. In theory less sugammadex would beneeded to neutralise the neuromuscular block if vecuronium was used to produce the neuromuscular block. Our aim was to compare reversal of vecuronium induced muscle relaxation between a new way of dosing sugammadex, which takes into account TOF value at the end of the surgery and the amount of vecuronium given during the surgery with neostigmine atropine combination. We also wanted to know how much this dosage regime can save compared to standard per kg dosage.Materials and Methods: 20 adult patients requiring a general anesthesia for surgery were analysed. The first group of 11 patients (SUG received sugammadex at the end of the surgery according to the table one for NMB reversal. The second group of 9 patients (NEO received neostigmine and atropine. Train of four (TOF value was recorded at the end of the surgery and then continuously until the TOF value reached more than 0.9 and the patient was extubated. The time required for the TOF value reaching 0.9 was compared between the groups. For economical evaluation we compared the amount of sugammadex used in the SUG group to standard sugammadex per kg dosage.Results and Discussion: Mean time to recovery to a TOF ratio of 0.9 with sugammadex was 5.12min versus 12.6 min with neostigmine atropine (P < 0.05. No sign of postoperative residual curarisation was observed in the SUG group. For patients in our study 530 mg of sugammadex were used to neutralise the NMB. If standard per kg sugammadex dosing had been used we would have used 2420 mg for the NMB reversal.Conclusion(s: New dosing for sugammadex was successful in neutralising the NMB regardlessof the TOF value

Stage specificity and dose-response relationships for chromosome aberrations induced in mouse primary spermatocytes following X-irradiation

Energy Technology Data Exchange (ETDEWEB)

Matsuda, Y.; Tobari, I.; Utsugi, T.

1986-05-01

In this study, dose-response relationships were examined for chromosome aberrations observed at diakinesis-metaphase I of spermatocytes with X-irradiation at various stages of meiosis (diplotene, mid-pachytene, zygotene and leptotene). The frequencies of cells with X-ray-induced chromosome aberrations increased with dose at all stages in the applied range of 0.5-3.0 Gy and tended to increase as the irradiated stages descended after leptotene stage. In three stages, the frequencies increased exponentially with dose, but the rates of induction of chromosome breaks were markedly different depending on the stages at which spermatocytes were irradiated with X-rays. The rate of induction was the highest at diplotene and the lowest at leptotene, suggesting that diplotene spermatocytes had the highest radiosensitivity to the induction of chromosome breaks, followed by pachytene, zygotene and leptotene spermatocytes in that order. The dose-response relationships fitted well to linear equations for deletion-type aberrations at each stage, and to linear-quadratic equations for exchange-type aberrations at all stages except for leptotene. At leptotene, the chromatid exchanges were hardly observed, the aberrations being mainly consisted of iso-chromatid fragments. On the contrary, chromatid exchanges and iso-chromatide deletions were mainly observed at later stages (zygotene-diplotene).

Dose-response effect of Red Maca (Lepidium meyenii) on benign prostatic hyperplasia induced by testosterone enanthate.

Science.gov (United States)

Gasco, M; Villegas, L; Yucra, S; Rubio, J; Gonzales, G F

2007-08-01

The main goal of this study was to determine the effect of a freeze-dried aqueous extract of the red variety of Lepidium meyenii (Red Maca) on testosterone-induced benign prostatic hyperplasia (BPH) in adult rats of the Holtzman strain. Rats were treated with freeze-dried aqueous extract of Red Maca at doses of 0, 0.01, 0.05, 0.1, and 0.5 g/kg body wt. A positive control group received Finasteride (0.6 mg/kg body wt.). After treatment, the animals were sacrificed, and the ventral prostate was extracted, and weighed. HPLC was used to determine the presence of glucosinolates in Red Maca. The prostate weight diminished in a dose-dependent fashion in rats treated with Red Maca. The effect of Red Maca was better than that observed with Finasteride. Finasteride, but not Red Maca, reduced seminal vesicles weight. Analysis of the HPLC indicated the presence of benzyl glucosinolate (Glucotropaeolin) with a content of 0.639%. Serum testosterone levels were not affected by Red Maca. Moreover, serum testosterone levels were not related to prostate or seminal vesicles weight in rats treated with vehicle and Red Maca. In conclusion, Red Maca administered orally in rats seems to exert an inhibitory effect at a level post DHT conversion, on the BPH-induced experimentally, although a direct measure of reductase action would still be required.

Radiation-Induced Rib Fractures After Hypofractionated Stereotactic Body Radiation Therapy: Risk Factors and Dose-Volume Relationship

Energy Technology Data Exchange (ETDEWEB)

Asai, Kaori [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Shioyama, Yoshiyuki, E-mail: shioyama@radiol.med.kyushu-u.ac.jp [Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Nakamura, Katsumasa; Sasaki, Tomonari; Ohga, Saiji; Nonoshita, Takeshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Yoshitake, Tadamasa [Department of Heavy Particle Therapy and Radiation Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Ohnishi, Kayoko [Department of Radiology, National Center for Global Health and Medicine, Tokyo (Japan); Terashima, Kotaro; Matsumoto, Keiji [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Hirata, Hideki [Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan)

2012-11-01

Purpose: The purpose of this study was to clarify the incidence, the clinical risk factors, and the dose-volume relationship of radiation-induced rib fracture (RIRF) after hypofractionated stereotactic body radiation therapy (SBRT). Methods and Materials: One hundred sixteen patients treated with SBRT for primary or metastatic lung cancer at our institution, with at least 6 months of follow-up and no previous overlapping radiation exposure, were included in this study. To determine the clinical risk factors associated with RIRF, correlations between the incidence of RIRF and the variables, including age, sex, diagnosis, gross tumor volume diameter, rib-tumor distance, and use of steroid administration, were analyzed. Dose-volume histogram analysis was also conducted. Regarding the maximum dose, V10, V20, V30, and V40 of the rib, and the incidences of RIRF were compared between the two groups divided by the cutoff value determined by the receiver operating characteristic curves. Results: One hundred sixteen patients and 374 ribs met the inclusion criteria. Among the 116 patients, 28 patients (46 ribs) experienced RIRF. The estimated incidence of rib fracture was 37.7% at 3 years. Limited distance from the rib to the tumor (<2.0 cm) was the only significant risk factor for RIRF (p = 0.0001). Among the dosimetric parameters used for receiver operating characteristic analysis, the maximum dose showed the highest area under the curve. The 3-year estimated risk of RIRF and the determined cutoff value were 45.8% vs. 1.4% (maximum dose, {>=}42.4 Gy or less), 51.6% vs. 2.0% (V40, {>=}0.29 cm{sup 3} or less), 45.8% vs. 2.2% (V30, {>=}1.35 cm{sup 3} or less), 42.0% vs. 8.5% (V20, {>=}3.62 cm{sup 3} or less), or 25.9% vs. 10.5% (V10, {>=}5.03 cm{sup 3} or less). Conclusions: The incidence of RIRF after hypofractionated SBRT is relatively high. The maximum dose and high-dose volume are strongly correlated with RIRF.

Dose rate effect on low-dose hyper-radiosensitivity with cells in vitro

Energy Technology Data Exchange (ETDEWEB)

Kim, Geon-Min; Kim, Eun-Hee [Seoul National University, Seoul (Korea, Republic of)

2016-10-15

Low-dose hyper-radiosensitivity (HRS) is the phenomenon that mammalian cells exhibit higher sensitivity to radiation at low doses (< 0.5 Gy) than expected by the linear-quadratic model. At doses above 0.5Gy, the cellular response is recovered to the level expected by the linear-quadratic model. This transition is called the increased radio-resistance (IRR). HRS was first verified using Chinese hamster V79 cells in vitro by Marples and has been confirmed in studies with other cell lines including human normal and tumor cells. HRS is known to be induced by inactivation of ataxia telangiectasia-mutated (ATM), which plays a key role in repairing DNA damages. Considering the connection between ATM and HRS, one can infer that dose rate may affect cellular response regarding HRS at low doses. In this study, we quantitated the effect of dose rate on HRS by clonogenic assay with normal and tumor cells. The HRS of cells at low dose exposures is a phenomenon already known. In this study, we observed HRS of rat normal diencephalon cells and rat gliosarcoma cells at doses below 1 Gy. In addition, we found that dose rate mattered. HRS occurred at low doses, but only when total dose was delivered at a rate below certain level.

Analysis of functional failure mode of commercial deep sub-micron SRAM induced by total dose irradiation

International Nuclear Information System (INIS)

Zheng Qi-Wen; Cui Jiang-Wei; Zhou Hang; Yu De-Zhao; Yu Xue-Feng; Lu Wu; Guo Qi; Ren Di-Yuan

2015-01-01

Functional failure mode of commercial deep sub-micron static random access memory (SRAM) induced by total dose irradiation is experimentally analyzed and verified by circuit simulation. We extensively characterize the functional failure mode of the device by testing its electrical parameters and function with test patterns covering different functional failure modes. Experimental results reveal that the functional failure mode of the device is a temporary function interruption caused by peripheral circuits being sensitive to the standby current rising. By including radiation-induced threshold shift and off-state leakage current in memory cell transistors, we simulate the influence of radiation on the functionality of the memory cell. Simulation results reveal that the memory cell is tolerant to irradiation due to its high stability, which agrees with our experimental result. (paper)

Adalimumab dose escalation and dose de-escalation success rate and predictors in a large national cohort of Crohn's patients

NARCIS (Netherlands)

Baert, Filip; Glorieus, Elien; Reenaers, Cathérine; D'Haens, Geert; Peeters, Harald; Franchimont, Dennis; Dewit, Olivier; Caenepeel, Philippe; Louis, Edouard; van Assche, Gert; D'Heygere, F.; George, C.; van Hootegem, P.; Ilegems, S.; Fontaine, F.; Colard, A.; Schoofs, N.; Belaiche, J.; Louis, E.; Reenaers, C.; van Kemseke, C.; Coche, J. C.; Dewit, O.; Rahier, J. F.; de Reuck, M.; Baert, F.; Decaestecker, J.; de Wulf, D.; Amininejad, L.; Franchimont, D.; van Gossum, A.; Du Ville, L.; Hendrickx, K.; Lepoutre, L.; Vandervoort, J.; van der Spek, P.; Sprengers, D.; van de Mierop, F.; Potvin, P.; Bontems, P.; Moreels, T.; van Outryve, M.; Mana, F.; de Looze, D.; de Vos, M.; Peeters, H.; Ferrante, M.; Rutgeerts, P.; van Assche, G.; Vermeire, S.

2013-01-01

Adalimumab is efficacious in inducing and maintaining remission in Crohn's disease but dose escalation is needed in 30-40% after 1 year. Attempts for dose de-escalation have not been studied. This study aimed to assess the need for, predictors, and outcome of dose escalation and de-escalation in a

The effect of radiosensitizers on the survival response of hypoxic mammalian cells: The low X-ray dose region, hypersensitivity and induced radioresistance

International Nuclear Information System (INIS)

Skov, K.A.; MacPhail, H.S.; Marples, B.

1994-01-01

It has been shown previously that the extent of chemical modification of the hypoxic radiation response is dependent on dose. Some types of sensitizer are more effective at low doses (to 4 Gy) than at higher doses. Since such drugs are possible adjuvants to radiotherapy, the mechanisms responsible for the variable response at clinical doses are summarized, and the effects of cisplatin and buthionine sulfoximine on the purported induced response to radiation in hypoxic cells are presented. Cisplatin at a low, nontoxic concentration (1 μM) appears to abolish the increased radioresistant portion of the survival response. A role for high-mobility-group protein binding by platinum drugs is hypothesized to explain their interaction with radiation, and conversely, it is suggested that the heretofore unexplained different behavior of certain hypoxic sensitizers at low doses could be, at least in part, an effect on the induction of resistance. 36 refs., 2 figs

SU-F-J-221: Adjusted Dose and Its Relation to Radiation Induced Liver Disease During Hepatocellular Carcinoma Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Huang, P; Gang, Y; Qin, S; Li, D [Shandong Province Key Laboratory of Medical Physics and Image Processing Technology, School of Physics and Electronics, Shandong Normal University (China); Li, H; Chen, J; Ma, C; Yin, Y [Department of Radiation Oncology, Shandong Cancer Hospital and Institute (China)

2016-06-15

Purpose: Many patients with hepatocellular carcinoma (HCC) had hepatic anatomy variations as a result of inter-fraction deformation during fractionated radiotherapy, which may result in difference from the planned dose. This study aimed to investigate the relationship between adjusted dose and radiation induced liver disease (RILD) in HCC patients receiving three dimensional conformal radiotherapy (3DCRT). Methods: Twenty-three HCC patients received conventional fractionated 3DCRT were enrolled in this retrospective investigation. Among them, seven patients had been diagnosed of RILD post-radiotherapy, including 4 cases of grade 2, 3 cases of grade 3 according to the CTCAE Version 3.0. Daily cone-beam CT (CBCT) scans were acquired throughout the whole treatment course for each patient. To reconstruct the daily dose to a patient considering the interfraction anatomy variations, the planned beams from each patient’s treatment plan were firstly applied to each daily modified CBCT (mCBCT). The daily doses were then summed together with the help of deformable image registration (DIR) to obtain the adjusted dose (Dadjusted) of the patient. Finally, the dose changes in normal liver between planned dose (Dplan) and Dadjusted were evaluated by V20, V30, V40 and the mean dose to normal liver (MDTNL). Univariate analysis was performed to identify the significant dose changes. Results: Among the twenty-three patients, the adjusted liver V20, V30, V40 and MDTNL showed significant changes from the planned ones (p<0.05) and averagely increased by 4.1%, 4.7%, 4.5% and 3.9Gy, respectively. And the adjusted liver dose in twenty-one patients (91%) were higher than planned value, the adjusted dose of patients with RILD (6/7) exceeds to the hepatic radiation tolerance. Conclusion: The adjusted dose of all the studied patients significantly differs from planned dose, and mCBCT-based dose reconstruction can aid in evaluating the robustness of the planning solutions, and adjusted dose

Enrofloxacin in therapeutic doses alters cytokine production by porcine PBMCs induced by lipopolysaccharide.

Science.gov (United States)

Pomorska-Mól, Małgorzata; Czyżewska-Dors, Ewelina; Kwit, Krzysztof; Pejsak, Zygmunt

2017-07-01

The effect of enrofloxacin on cytokine secretion by porcine peripheral blood mononuclear cells (PBMCs) was studied. Twenty 8-20-week-old pigs were randomly divided into two groups: control (C, n = 10) and experimental (E, n = 10) were used. Pigs from group E received enrofloxacin at therapeutic dose for 5 consecutive days. Blood samples were collected at 0 (before antibiotic administration), 2, 4 (during antibiotic therapy) 6, 9, 14 21, 35, 49, and 63 d of study (after treatment). PBMCs of pigs from both groups were incubated with or without lipopolysaccharide (LPS). Ex vivo production on interleukin (IL)-4, IL-6, IL-10, INF-γ, and TNF-α were analyzed using ELISA assay. Intramuscular administration of enrofloxacin to healthy pigs for 5 consecutive days induced a transitory reduction of the ex vivo response of PBMCs to LPS in terms of IL-6 and TNF-α secretion. The level of IL-6 returned to day 0 level shortly after end of treatment, while the TNF-α production remained reduced 10 d after the end of treatment. Our results indicate that enrofloxacin given in vivo in therapeutic doses has an immunomodulatory effect through its capacity to inhibit ex vivo secretion of IL-6 and TNF-α by porcine PBMC after LPS stimulation.

Superantigen-Induced Cytokine Release from Whole-Blood Cell Culture as a Functional Measure of Drug Efficacy after Oral Dosing in Nonhuman Primates

National Research Council Canada - National Science Library

Krakauer, Teresa; Stephens, Julie; Buckley, Marilyn; Tate, Mallory

2007-01-01

...) closely resemble humans. We examined the ex vivo cytokine response of superantigen-stimulated whole-blood cells as a first step to therapeutic efficacy testing for bacterial superantigen-induced shock in NHP after oral dosing of pentoxifylline...

Radiobiological responses for two cell lines following continuous low dose-rate (CLDR) and pulsed dose rate (PDR) brachytherapy

International Nuclear Information System (INIS)

Hanisch, Per Henrik; Furre, Torbjoern; Olsen, Dag Rune; Pettersen, Erik O.

2007-01-01

The iso-effective irradiation of continuous low-dose-rate (CLDR) irradiation was compared with that of various schedules of pulsed dose rate (PDR) irradiation for cells of two established human lines, T-47D and NHIK 3025. Complete single-dose response curves were obtained for determination of parameters α and β by fitting of the linear quadratic formula. Sublethal damage repair constants μ and T 1/2 were determined by split-dose recovery experiments. On basis of the acquired parameters of each cell type the relative effectiveness of the two regimens of irradiation (CLDR and PDR) was calculated by use of Fowler's radiobiological model for iso-effect irradiation for repeated fractions of dose delivered at medium dose rates. For both cell types the predicted and observed relative effectiveness was compared at low and high iso-effect levels. The results indicate that the effect of PDR irradiation predicted by Fowler's model is equal to that of CLDR irradiation for both small and large doses with T-47D cells. With NHIK 3025 cells PDR irradiation induces a larger effect than predicted by the model for small doses, while it induces the predicted effect for high doses. The underlying cause of this difference is unclear, but cell-cycle parameters, like G2-accumulation is tested and found to be the same for the two cell lines

Radiation doses in interventional neuroradiology

International Nuclear Information System (INIS)

Theodorakou, C.; Butler, P.; Horrocks, J.A.

2001-01-01

Patient radiation doses during interventional radiology (IR) procedures may reach the thresholds for radiation-induced skin and eye lens injuries. This study investigates the radiation doses received by patients undergoing cerebral embolization. Measurements were conducted using thermoluminescent dosimeters. Radiotherapy verification films were used in order to visualise the radiation field. For each procedure the fluoroscopic and digital dose-area product, the fluoroscopic time, the total number of acquired images and entrance-skin dose calculated by the angiographic unit were recorded. In this paper, the skin, eye and thyroid glands doses on a sample of patients are presented. From a preliminary study of 13 patients having undergone cerebral embolization, it was deduced that six of them have received a dose above 1 Gy. Detailed dose data from patients undergoing IR procedures will be collected in the future with the aim of developing a model to allow estimation of the dose prior to the procedure as well as to look at techniques of dose reduction. (author)

The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

International Nuclear Information System (INIS)

Ali, Haytham; Galal, Omima; Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan; Abdelrahim, Eman; Ono, Yusuke; Mostafa, Emtethal; Li, Tao-Sheng

2014-01-01

Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit + stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit + stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit + stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms

The potential benefits of nicaraven to protect against radiation-induced injury in hematopoietic stem/progenitor cells with relative low dose exposures

Energy Technology Data Exchange (ETDEWEB)

Ali, Haytham [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Galal, Omima [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Urata, Yoshishige; Goto, Shinji; Guo, Chang-Ying; Luo, Lan [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Abdelrahim, Eman [Department of Medical Histology, Qena Faculty of Medicine, South Valley University (Egypt); Ono, Yusuke [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Mostafa, Emtethal [Department of Medical Physiology and Cell Biology, Qena Faculty of Medicine, South Valley University (Egypt); Li, Tao-Sheng, E-mail: litaoshe@nagasaki-u.ac.jp [Department of Stem Cell Biology, Atomic Bomb Disease Institute, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

2014-09-26

Highlights: • Nicaraven mitigated the radiation-induced reduction of c-kit{sup +} stem cells. • Nicaraven enhanced the function of hematopoietic stem/progenitor cells. • Complex mechanisms involved in the protection of nicaraven to radiation injury. - Abstract: Nicaraven, a hydroxyl radical-specific scavenger has been demonstrated to attenuate radiation injury in hematopoietic stem cells with 5 Gy γ-ray exposures. We explored the effect and related mechanisms of nicaraven for protecting radiation injury induced by sequential exposures to a relatively lower dose γ-ray. C57BL/6 mice were given nicaraven or placebo within 30 min before exposure to 50 mGy γ-ray daily for 30 days in sequences (cumulative dose of 1.5 Gy). Mice were victimized 24 h after the last radiation exposure, and the number, function and oxidative stress of hematopoietic stem cells were quantitatively estimated. We also compared the gene expression in these purified stem cells from mice received nicaraven and placebo treatment. Nicaraven increased the number of c-kit{sup +} stem/progenitor cells in bone marrow and peripheral blood, with a recovery rate around 60–90% of age-matched non-irradiated healthy mice. The potency of colony forming from hematopoietic stem/progenitor cells as indicator of function was completely protected with nicaraven treatment. Furthermore, nicaraven treatment changed the expression of many genes associated to DNA repair, inflammatory response, and immunomodulation in c-kit{sup +} stem/progenitor cells. Nicaraven effectively protected against damages of hematopoietic stem/progenitor cells induced by sequential exposures to a relatively low dose radiation, via complex mechanisms.

Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

Science.gov (United States)

Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

2018-03-24

Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

Evaluation of changes in serum chemistry in association with feed withdrawal or high dose oral gavage with Dextran Sodium Sulfate (DSS) induced gut leakage in broiler chickens

Science.gov (United States)

Dextran sodium sulfate (DSS) has been shown to be effective at inducing enteric inflammation in broiler chickens, resulting in increased leakage of orally administered fluorescein isothiocyanate dextran to circulation. In a previous study, two doses of DSS (0.45g/dose) administered as oral gavage re...

Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects.

Science.gov (United States)

Palttala, Iida; Heinämäki, Jyrki; Honkanen, Outi; Suominen, Risto; Antikainen, Osmo; Hirvonen, Jouni; Yliruusi, Jouko

2013-03-01

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.

Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

International Nuclear Information System (INIS)

Nomura, Takaharu

2008-01-01

Living organisms have developed complex biological system which protects themselves against environmental radiation, and irradiation with proper dose, dose-rate and irradiation time can stimulate their biological responses against oxidative stress evoked by the irradiation. Because reactive oxygen species are involved in various human diseases, non-toxic low dose/low dose-rate radiation can be utilized for the amelioration of such diseases. In this study, we used mouse experimental models for fatty liver, nephritis, diabetes, and ageing to elucidate the ameliorative effect of low dose/low dose-rate radiation in relation to endogenous antioxidant activity. Single irradiation at 0.5 Gy ameliorates carbon tetrachloride-induced fatty liver. The irradiation increases hepatic anti-oxidative system involving glutathione and glutathione peroxidase, suggesting that endogenous radical scavenger is essential for the ameliorative effect of low dose radiation on carbon tetrachloride-induced fatty liver. Single irradiation at 0.5 Gy ameliorates ferric nitrilotriacetate-induced nephritis. The irradiation increases catalase and decreases superoxide dismutase in kidney. The result suggests that low dose radiation reduced generation of hydroxide radical generation by reducing cellular hydroperoxide level. Single irradiation at 0.5 Gy at 12 week of age ameliorates incidence of type I diabetes in non-obese diabetic (NOD) mice through the suppression of inflammatory activity of splenocytes, and resultant apoptosis of β-cells in pancreas. The irradiation activities of superoxide dismutase and catalase, which coordinately diminish intracellular reactive oxygen species. Continuous irradiation at 0.70 mGy/hr from 10 week of age elongates life span, and suppresses alopecia in type II diabetesmice. The irradiation improved glucose clearance without affecting insulin-resistance, and increased pancreatic catalase activity. The results suggest that continuous low dose-rate irradiation protect

Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells.

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Pustovalova, Margarita; Astrelina, Тatiana A; Grekhova, Anna; Vorobyeva, Natalia; Tsvetkova, Anastasia; Blokhina, Taisia; Nikitina, Victoria; Suchkova, Yulia; Usupzhanova, Daria; Brunchukov, Vitalyi; Kobzeva, Irina; Karaseva, Тatiana; Ozerov, Ivan V; Samoylov, Aleksandr; Bushmanov, Andrey; Leonov, Sergey; Izumchenko, Evgeny; Zhavoronkov, Alex; Klokov, Dmitry; Osipov, Andreyan N

2017-11-21

Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γН2АХ foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γН2АХ foci still present at 24 h. Notably, these low dose induced residual γН2АХ foci were not co-localized with рАТМ foci and were observed predominantly in the proliferating Кi67 positive (Кi67+) cells. The number of γН2АХ foci and the fraction of nonproliferating (Кi67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γН2АХ foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AХ foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.

Modifications in the optical and thermal properties of a CR-39 polymeric detector induced by high doses of γ-radiation

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Saad, A. F.; Ibraheim, Mona H.; Nwara, Aya M.; Kandil, S. A.

2018-04-01

Effects of γ-radiation on the optical and thermal properties of a poly allyl diglycol carbonate (PADC), a form of CR-39, polymer have been investigated. CR-39 detectors were exposed to γ-rays at very high doses ranging from 5.0 × 105 to 3.0 × 106 Gy. The induced changes were analyzed using ultraviolet-visible spectroscopy (UV-VIS) in absorbance mode, and thermogravimetric analysis (TGA). The UV-visible spectra of the virgin and γ-irradiated CR-39 polymer detectors displayed a significant decreasing trend in their optical energy band gaps for indirect transitions, whereas for the direct ones showed a little change. This drop in the energy band gap with increasing dose is discussed on the basis of the gamma irradiation induced modifications in the CR-39 polymeric detector. The TGA thermograms show that the weight loss rate increased with increase in dose, which may be due to the disordered system via scission followed by crosslinking in the irradiated polymer detector. The TGA thermograms also indicated that the CR-39 detector decomposed in three/four stages for the virgin and irradiated samples. The activation energy for thermal decomposition was determined using a type of Arrhenius equation based on the TGA experimental results. These experimental results so obtained can be well used in radiation dosimetry.

Pb low doses induced genotoxicity in Lactuca sativa plants.

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Silva, S; Silva, P; Oliveira, H; Gaivão, I; Matos, M; Pinto-Carnide, O; Santos, C

2017-03-01

Soil and water contamination by lead (Pb) remains a topic of great concern, particularly regarding crop production. The admissible Pb values in irrigation water in several countries range from ≈0.1 to ≈5 mg L -1 . In order to evaluate putative effects of Pb within legal doses on crops growth, we exposed Lactuca sativa seeds and seedlings to increasing doses of Pb(NO 3 ) 2 up to 20 mg L -1 . The OECD parameter seed germination and seedling/plant growth were not affected by any of the Pb-concentrations used. However, for doses higher than 5 mg L -1 significant DNA damage was detected: Comet assay detected DNA fragmentation at ≥ 5 mg L -1 and presence of micronuclei (MN) were detected for 20 mg L -1 . Also, cell cycle impairment was observed for doses as low as 0.05 mg L -1 and 0.5 mg L -1 (mostly G 2 arrest). Our data show that for the low doses of Pb used, the OECD endpoints were not able to detect toxicity, while more sensitive endpoints (related with DNA damage and mitotic/interphase disorders) identified genotoxic and cytostatic effects. Furthermore, the nature of the genotoxic effect was dependent on the concentration. Finally, we recommend that MN test and the comet assay should be included as sensitive endpoints in (eco)toxicological assays. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

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2011-01-01

Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p.) 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.). IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v.) prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical) given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA. PMID:22114930

Increased interleukin-1β levels following low dose MDMA induces tolerance against the 5-HT neurotoxicity produced by challenge MDMA

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Mayado Andrea

2011-11-01

Full Text Available Abstract Background Preconditioning is a phenomenon by which tolerance develops to injury by previous exposure to a stressor of mild severity. Previous studies have shown that single or repeated low dose MDMA can attenuate 5-HT transporter loss produced by a subsequent neurotoxic dose of the drug. We have explored the mechanism of delayed preconditioning by low dose MDMA. Methods Male Dark Agouti rats were given low dose MDMA (3 mg/kg, i.p. 96 h before receiving neurotoxic MDMA (12.5 mg/kg, i.p.. IL-1β and IL1ra levels and 5-HT transporter density in frontal cortex were quantified at 1 h, 3 h or 7 days. IL-1β, IL-1ra and IL-1RI were determined between 3 h and 96 h after low dose MDMA. sIL-1RI combined with low dose MDMA or IL-1β were given 96 h before neurotoxic MDMA and toxicity assessed 7 days later. Results Pretreatment with low dose MDMA attenuated both the 5-HT transporter loss and elevated IL-1β levels induced by neurotoxic MDMA while producing an increase in IL-1ra levels. Low dose MDMA produced an increase in IL-1β at 3 h and in IL-1ra at 96 h. sIL-1RI expression was also increased after low dose MDMA. Coadministration of sIL-1RI (3 μg, i.c.v. prevented the protection against neurotoxic MDMA provided by low dose MDMA. Furthermore, IL-1β (2.5 pg, intracortical given 96 h before neurotoxic MDMA protected against the 5-HT neurotoxicity produced by the drug, thus mimicking preconditioning. Conclusions These results suggest that IL-1β plays an important role in the development of delayed preconditioning by low dose MDMA.

Intradermal inactivated poliovirus vaccine: a preclinical dose-finding study.

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Kouiavskaia, Diana; Mirochnitchenko, Olga; Dragunsky, Eugenia; Kochba, Efrat; Levin, Yotam; Troy, Stephanie; Chumakov, Konstantin

2015-05-01

Intradermal delivery of vaccines has been shown to result in dose sparing. We tested the ability of fractional doses of inactivated poliovirus vaccine (IPV) delivered intradermally to induce levels of serum poliovirus-neutralizing antibodies similar to immunization through the intramuscular route. Immunogenicity of fractional doses of IPV was studied by comparing intramuscular and intradermal immunization of Wistar rats using NanoPass MicronJet600 microneedles. Intradermal delivery of partial vaccine doses induced antibodies at titers comparable to those after immunization with full human dose delivered intramuscularly. The results suggest that intradermal delivery of IPV may lead to dose-sparing effect and reduction of the vaccination cost. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Quantitative analysis of biological responses to low dose-rate γ-radiation, including dose, irradiation time, and dose-rate

International Nuclear Information System (INIS)

Magae, J.; Furukawa, C.; Kawakami, Y.; Hoshi, Y.; Ogata, H.

2003-01-01

Full text: Because biological responses to radiation are complex processes dependent on irradiation time as well as total dose, it is necessary to include dose, dose-rate and irradiation time simultaneously to predict the risk of low dose-rate irradiation. In this study, we analyzed quantitative relationship among dose, irradiation time and dose-rate, using chromosomal breakage and proliferation inhibition of human cells. For evaluation of chromosome breakage we assessed micronuclei induced by radiation. U2OS cells, a human osteosarcoma cell line, were exposed to gamma-ray in irradiation room bearing 50,000 Ci 60 Co. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, cytoplasm and nucleus were stained with DAPI and propidium iodide, and the number of binuclear cells bearing micronuclei was determined by fluorescent microscopy. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [3H] thymidine was pulsed for 4 h before harvesting. Dose-rate in the irradiation room was measured with photoluminescence dosimeter. While irradiation time less than 24 h did not affect dose-response curves for both biological responses, they were remarkably attenuated as exposure time increased to more than 7 days. These biological responses were dependent on dose-rate rather than dose when cells were irradiated for 30 days. Moreover, percentage of micronucleus-forming cells cultured continuously for more than 60 days at the constant dose-rate, was gradually decreased in spite of the total dose accumulation. These results suggest that biological responses at low dose-rate, are remarkably affected by exposure time, that they are dependent on dose-rate rather than total dose in the case of long-term irradiation, and that cells are getting resistant to radiation after the continuous irradiation for 2 months. It is necessary to include effect of irradiation time and dose-rate sufficiently to evaluate risk

Integral Dose and Radiation-Induced Secondary Malignancies: Comparison between Stereotactic Body Radiation Therapy and Three-Dimensional Conformal Radiotherapy

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Stefano G. Masciullo

2012-11-01

Full Text Available The aim of the present paper is to compare the integral dose received by non-tumor tissue (NTID in stereotactic body radiation therapy (SBRT with modified LINAC with that received by three-dimensional conformal radiotherapy (3D-CRT, estimating possible correlations between NTID and radiation-induced secondary malignancy risk. Eight patients with intrathoracic lesions were treated with SBRT, 23 Gy × 1 fraction. All patients were then replanned for 3D-CRT, maintaining the same target coverage and applying a dose scheme of 2 Gy × 32 fractions. The dose equivalence between the different treatment modalities was achieved assuming α/β = 10Gy for tumor tissue and imposing the same biological effective dose (BED on the target (BED = 76Gy10. Total NTIDs for both techniques was calculated considering α/β = 3Gy for healthy tissue. Excess absolute cancer risk (EAR was calculated for various organs using a mechanistic model that includes fractionation effects. A paired two-tailed Student t-test was performed to determine statistically significant differences between the data (p ≤ 0.05. Our study indicates that despite the fact that for all patients integral dose is higher for SBRT treatments than 3D-CRT (p = 0.002, secondary cancer risk associated to SBRT patients is significantly smaller than that calculated for 3D-CRT (p = 0.001. This suggests that integral dose is not a good estimator for quantifying cancer induction. Indeed, for the model and parameters used, hypofractionated radiotherapy has the potential for secondary cancer reduction. The development of reliable secondary cancer risk models seems to be a key issue in fractionated radiotherapy. Further assessments of integral doses received with 3D-CRT and other special techniques are also strongly encouraged.

Characterizing low dose and dose rate effects in rodent and human neural stem cells exposed to proton and gamma irradiation

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Bertrand P. Tseng

2013-01-01

Full Text Available Past work has shown that exposure to gamma rays and protons elicit a persistent oxidative stress in rodent and human neural stem cells (hNSCs. We have now adapted these studies to more realistic exposure scenarios in space, using lower doses and dose rates of these radiation modalities, to further elucidate the role of radiation-induced oxidative stress in these cells. Rodent neural stem and precursor cells grown as neurospheres and human neural stem cells grown as monolayers were subjected to acute and multi-dosing paradigms at differing dose rates and analyzed for changes in reactive oxygen species (ROS, reactive nitrogen species (RNS, nitric oxide and superoxide for 2 days after irradiation. While acute exposures led to significant changes in both cell types, hNSCs in particular, exhibited marked and significant elevations in radiation-induced oxidative stress. Elevated oxidative stress was more significant in hNSCs as opposed to their rodent counterparts, and hNSCs were significantly more sensitive to low dose exposures in terms of survival. Combinations of protons and γ-rays delivered as lower priming or higher challenge doses elicited radioadaptive changes that were associated with improved survival, but in general, only under conditions where the levels of reactive species were suppressed compared to cells irradiated acutely. Protective radioadaptive effects on survival were eliminated in the presence of the antioxidant N-acetylcysteine, suggesting further that radiation-induced oxidative stress could activate pro-survival signaling pathways that were sensitive to redox state. Data corroborates much of our past work and shows that low dose and dose rate exposures elicit significant changes in oxidative stress that have functional consequences on survival.

Immune cell-derived c3 is required for autoimmune diabetes induced by multiple low doses of streptozotocin.

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Lin, Marvin; Yin, Na; Murphy, Barbara; Medof, M Edward; Segerer, Stephan; Heeger, Peter S; Schröppel, Bernd

2010-09-01

The complement system contributes to autoimmune injury, but its involvement in promoting the development of autoimmune diabetes is unknown. In this study, our goal was to ascertain the role of complement C3 in autoimmune diabetes. Susceptibility to diabetes development after multiple low-dose streptozotocin treatment in wild-type (WT) and C3-deficient mice was analyzed. Bone marrow chimeras, luminex, and quantitative reverse transcription PCR assays were performed to evaluate the phenotypic and immunologic impact of C3 in the development of this diabetes model. Coincident with the induced elevations in blood glucose levels, we documented alternative pathway complement component gene expression within the islets of the diabetic WT mice. When we repeated the experiments with C3-deficient mice, we observed complete resistance to disease, as assessed by the absence of histologic insulitis and the absence of T-cell reactivity to islet antigens. Studies of WT chimeras bearing C3-deficient bone marrow cells showed that bone marrow cell-derived C3, and not serum C3, is involved in the induction of diabetes in this model. The data reveal a key role for immune cell-derived C3 in the pathogenesis of murine multiple low-dose streptozotocin-induced diabetes and support the concept that immune cell mediated diabetes is in part complement-dependent.

The researches on the effects of low doses irradiation

International Nuclear Information System (INIS)

2009-02-01

All research conducted as part of 'Risc-Rad' and those conducted by actors in international programs on low doses allow progress in understanding mechanisms of carcinogenesis associated with irradiation. The data do not question the use in radiation protection, risk estimation models based on a linear increase of the risk with the dose of radiation. Nevertheless, they show that the nature of biological responses induced by low doses of radiation has differences with the responses induced by high doses of radiation. They also show the diversity of effects/dose relationships as the mechanism observed and the importance of genetic predisposition in the individual sensitivity to low doses of radiation. It is therefore essential to continue to bring new data to better understand the complex biological effects and their impact on the establishment of radiation protection standards. In addition, the results have often been at the cellular level. The diversity of responses induced by radiations is also a function of cell types observed, the aging of cells and tissue organization. It is essential to strengthen researches at the tissue and body level, involving in vitro and in vivo approaches while testing the hypothesis in epidemiology with a global approach to systems biology. Over the past four years, the collaboration between partners of 'Risc-Rad' using experimental biology approaches and those using mathematical modeling techniques aimed at developing a new model describing the carcinogenesis induced by low radiation doses. On an other hand, The High level expert group on European low dose risk research (H.L.E.G.) develop programmes in the area of low dose irradiation (Germany, Finland, France, Italy and United Kingdom). It proposed a structure of trans national government called M.E.L.O.D.I. ( multidisciplinary european low dose initiative). Its objective is to structure and integrate European research by gathering around a common programme of multidisciplinary

Induced terpene accumulation in Norway spruce inhibits bark beetle colonization in a dose-dependent manner.

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Tao Zhao

Full Text Available Tree-killing bark beetles (Coleoptera, Scolytinae are among the most economically and ecologically important forest pests in the northern hemisphere. Induction of terpenoid-based oleoresin has long been considered important in conifer defense against bark beetles, but it has been difficult to demonstrate a direct correlation between terpene levels and resistance to bark beetle colonization.To test for inhibitory effects of induced terpenes on colonization by the spruce bark beetle Ips typographus (L. we inoculated 20 mature Norway spruce Picea abies (L. Karsten trees with a virulent fungus associated with the beetle, Ceratocystis polonica (Siem. C. Moreau, and investigated induced terpene levels and beetle colonization in the bark.Fungal inoculation induced very strong and highly variable terpene accumulation 35 days after inoculation. Trees with high induced terpene levels (n = 7 had only 4.9% as many beetle attacks (5.1 vs. 103.5 attacks m(-2 and 2.6% as much gallery length (0.029 m m(-2 vs. 1.11 m m(-2 as trees with low terpene levels (n = 6. There was a highly significant rank correlation between terpene levels at day 35 and beetle colonization in individual trees. The relationship between induced terpene levels and beetle colonization was not linear but thresholded: above a low threshold concentration of ∼100 mg terpene g(-1 dry phloem trees suffered only moderate beetle colonization, and above a high threshold of ∼200 mg terpene g(-1 dry phloem trees were virtually unattacked.This is the first study demonstrating a dose-dependent relationship between induced terpenes and tree resistance to bark beetle colonization under field conditions, indicating that terpene induction may be instrumental in tree resistance. This knowledge could be useful for developing management strategies that decrease the impact of tree-killing bark beetles.

Comments on 'Reconsidering the definition of a dose-volume histogram'-dose-mass histogram (DMH) versus dose-volume histogram (DVH) for predicting radiation-induced pneumonitis

International Nuclear Information System (INIS)

Mavroidis, Panayiotis; Plataniotis, Georgios A; Gorka, Magdalena Adamus; Lind, Bengt K

2006-01-01

In a recently published paper (Nioutsikou et al 2005 Phys. Med. Biol. 50 L17) the authors showed that the use of the dose-mass histogram (DMH) concept is a more accurate descriptor of the dose delivered to lung than the traditionally used dose-volume histogram (DVH) concept. Furthermore, they state that if a functional imaging modality could also be registered to the anatomical imaging modality providing a functional weighting across the organ (functional mass) then the more general and realistic concept of the dose-functioning mass histogram (D[F]MH) could be an even more appropriate descriptor. The comments of the present letter to the editor are in line with the basic arguments of that work since their general conclusions appear to be supported by the comparison of the DMH and DVH concepts using radiobiological measures. In this study, it is examined whether the dose-mass histogram (DMH) concept deviated significantly from the widely used dose-volume histogram (DVH) concept regarding the expected lung complications and if there are clinical indications supporting these results. The problem was investigated theoretically by applying two hypothetical dose distributions (Gaussian and semi-Gaussian shaped) on two lungs of uniform and varying densities. The influence of the deviation between DVHs and DMHs on the treatment outcome was estimated by using the relative seriality and LKB models using the Gagliardi et al (2000 Int. J. Radiat. Oncol. Biol. Phys. 46 373) and Seppenwoolde et al (2003 Int. J. Radiat. Oncol. Biol. Phys. 55 724) parameter sets for radiation pneumonitis, respectively. Furthermore, the biological equivalent of their difference was estimated by the biologically effective uniform dose (D-bar) and equivalent uniform dose (EUD) concepts, respectively. It is shown that the relation between the DVHs and DMHs varies depending on the underlying cell density distribution and the applied dose distribution. However, the range of their deviation in terms of

Study on the evaluation of radiation doses in dental radiography. Doses and risks due to dental full mouth examination

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Sugimoto, K [Kanagawa Dental Coll., Yokosuka (Japan)

1980-09-01

Radiation doses and possible biological risks due to dental full mouth examination (adult: 10-film technique, child: 6-film technique) were evaluated based on preliminary experiments and statistical surveillance of patients' records. Dosimetrical studies were performed by using head and neck phantoms and a dental x-ray tube. Radiation doses were measured by x-ray films and thermoluminescence dosimeters. For the obtained doses of skin, eyes, thyroid gland and bone marrow, the biological risk of leukemia and thyroid cancer was discussed on the statistical basis of patients at Kanagawa Dental College Hospital. The major findings were as follows: The total number of patients who recieved full mouth x-ray examination at Kanagawa Dental College Hospital in 1978 was 1,099. The number of male patients was 382 (3,804 films) and that of female patients was 717 (7,138 films). In both sexes, the number of patients was the greatest in the group of 8 - 14 years of age. The collective doses of bone marrow due to full mouth 10-film examination performed at Kanagawa Dental College Hospital in 1978 were approximately 6.0 rad, which could induce leukemia with a probability of 1/8,000. The collective doses of thyroid gland were approximately 13 rad, which could induce lethal thyroid cancer with a probability of 1/15,000. The radiation dose due to the dental radiography for examination at Kanagawa Dental College Hospital was proved to be apparently below the level that could actually induce radiation injuries. But the collective radiation doses due to dental examination in Japan as a whole were approximately 8,000 times greater than that in Kanagawa Dental College Hospital.

Dose-rate effects on gamma-induced genetic injury in rat spermatogonia

International Nuclear Information System (INIS)

Vyglenov, A.

1990-01-01

Data for correlation between the reciprocal translocations (RT) yield in rat germ cells and the doses of 0.5 - 3.0 Gy are presented. A 60 Co source has been used with dose rates of 0.25, 8 x 10 -2 and 7 x 10 -3 Gy/min. The results from the cytogenetic analysis made 6 months after irradiation have shown an increase of the yield with the increase of the dose, which can be described as a linear unthreshold dependence. The dose rate effect is expressed in decrease of mutation frequency. The comparison with earlier author's data from similar experiments for acute irradiation allows to determine the RBE of gamma irradiation at the three dose rates investigated as 0.6, 0.2 and 0.1 respectively. The reported results are connected with the problem of variety specificity of the dose rate effect. 2 figs., 2 tabs., 15 refs

A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia

DEFF Research Database (Denmark)

Duvaldestin, Philippe; Kuizenga, Karel; Saldien, Vera

2010-01-01

Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular...

Dynamically accumulated dose and 4D accumulated dose for moving tumors

International Nuclear Information System (INIS)

Li Heng; Li Yupeng; Zhang Xiaodong; Li Xiaoqiang; Liu Wei; Gillin, Michael T.; Zhu, X. Ronald

2012-01-01

Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove the principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a “pulsed beam”; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a “continuous beam.” A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose

Imaging dose in breast radiotherapy: does breast size affect the dose to the organs at risk and the risk of secondary cancer to the contralateral breast?

International Nuclear Information System (INIS)

Batumalai, Vikneswary; Quinn, Alexandra; Jameson, Michael; Delaney, Geoff; Holloway, Lois

2015-01-01

Correct target positioning is crucial for accurate dose delivery in breast radiotherapy resulting in utilisation of daily imaging. However, the radiation dose from daily imaging is associated with increased probability of secondary induced cancer. The aim of this study was to quantify doses associated with three imaging modalities and investigate the correlation of dose and varying breast size in breast radiotherapy. Planning computed tomography (CT) data sets of 30 breast cancer patients were utilised to simulate the dose received by various organs from a megavoltage computed tomography (MV-CT), megavoltage electronic portal image (MV-EPI) and megavoltage cone-beam computed tomography (MV-CBCT). The mean dose to organs adjacent to the target volume (contralateral breast, lungs, spinal cord and heart) were analysed. Pearson correlation analysis was performed to determine the relationship between imaging dose and primary breast volume and the lifetime attributable risk (LAR) of induced secondary cancer was calculated for the contralateral breast. The highest contralateral breast mean dose was from the MV-CBCT (1.79 Gy), followed by MV-EPI (0.22 Gy) and MV-CT (0.11 Gy). A similar trend was found for all organs at risk (OAR) analysed. The primary breast volume inversely correlated with the contralateral breast dose for all three imaging modalities. As the primary breast volume increases, the likelihood of a patient developing a radiation-induced secondary cancer to the contralateral breast decreases. MV-CBCT showed a stronger relationship between breast size and LAR of developing a radiation-induced contralateral breast cancer in comparison with the MV-CT and MV-EPI. For breast patients, imaging dose to OAR depends on imaging modality and treated breast size. When considering the use of imaging during breast radiotherapy, the patient's breast size and contralateral breast dose should be taken into account

Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: Potential implications for neurodegenerative diseases.

Science.gov (United States)

Takser, Larissa; Benachour, Nora; Husk, Barry; Cabana, Hubert; Gris, Denis

2016-01-01

Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and neuroblastoma N2a cell lines. We tested cylindrospermopsin (CYN), microcystin-LR (MC-LR), and anatoxin-a (ATX-a), individually as well as their mixture. In addition, we studied the neurotoxins β- N -methylamino-l-alanine (BMAA) and its isomer 2,4-diaminobutyric acid (DAB), as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of caspases 3/7. Cell death and inflammation are the hallmarks of neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3-15 times more potent at inducing apoptosis and inflammation. Our results suggest that common cyanotoxins at low doses have a potential to induce inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food.

Dose rate and dose fractionation studies in total body irradiation of dogs

International Nuclear Information System (INIS)

Kolb, H.J.; Netzel, B.; Schaffer, E.; Kolb, H.

1979-01-01

Total body irradiation (TBI) with 800-900 rads and allogeneic bone marrow transplantation according to the regimen designated by the Seattle group has induced remissions in patients with otherwise refractory acute leukemias. Relapse of leukemia after bone marrow transplantation remains the major problem, when the Seattle set up of two opposing 60 Co-sources and a low dose rate is used in TBI. Studies in dogs with TBI at various dose rates confirmed observations in mice that gastrointestinal toxicity is unlike toxicity against hemopoietic stem cells and possibly also leukemic stem cells depending on the dose rate. However, following very high single doses (2400 R) and marrow infusion acute gastrointestinal toxicity was not prevented by the lowest dose rate studied (0.5 R/min). Fractionated TBI with fractions of 600 R in addition to 1200 R (1000 rads) permitted the application of total doses up to 300 R followed by marrow infusion without irreversible toxicity. 26 dogs given 2400-3000 R have been observed for presently up to 2 years with regard to delayed radiation toxicity. This toxicity was mild in dogs given single doses at a low dose rate or fractionated TBI. Fractionated TBI is presently evaluated with allogeneic transplants in the dog before being applied to leukemic patients

Metabolism and binding to DNA of a novel hepatocarcinogen: methapyrilene

International Nuclear Information System (INIS)

Lampe, M.A.

1987-01-01

The purpose of this study was to characterize the metabolism and macromolecular binding of [ 14 C]-MPH. When rats were treated for up to sixteen weeks with 1000 ppm MPH, they excreted at least six MPH related compounds in their urine including 2-hydroxymethyl-thiophene, N-2-pyridyl-N'-dimethylethylenediamine, (5-hydroxypyridyl)methapyrilene, (5-hydroxypyridyl)N-2-pyridyl-N'-dimethylethylenediamine and MPH. In vitro metabolism is also affected by chronic treatment of rats with MPH, with the most remarkable change observed being an increase in the mass balance to approximately 100% after 8 or 16 weeks pretreatment. Metabolism of MPH by rat liver microsomes is dependent on the activity of cytochrome P-450 enzymes, as metabolism in vitro was inhibited by the addition 2,4-dichloro-6-phenylphenoxyethylamine (DPEA) and 2-diethylaminoethyl-2,2-diphenylvalerate (SKF-525A). Treatment of rats with phenobarbital or 3-methylcholanthrene induced metabolism of MPH while pretreatment of rats with isosafole or pregnenolone-16α-carbonitrile had a more selective effect on MPH metabolism, and only increased the formation of methapyrilene-amide

Intervention effect and dose-dependent response of tanreqing injection on airway inflammation in lipopolysaccharide-induced rats.

Science.gov (United States)

Dong, Shoujin; Zhong, Yunqing; Yang, Kun; Xiong, Xiaoling; Mao, Bing

2013-08-01

To assess the effect of Tanreqing injection on airway inflammation in rats. A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-13, cytokine-induced neutrophil chemoat-tractant-1, and tumor necrosis factor-alpha were measured using enzyme linked immunosorbent assay. The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

Cytogenetic effects of low-dose radiation

International Nuclear Information System (INIS)

Metalli, P.

1983-01-01

The effects of ionizing radiation on chromosomes have been known for several decades and dose-effect relationships are also fairly well established in the mid- and high-dose and dose-rate range for chromosomes of mammalian cells. In the range of low doses and dose rates of different types of radiation few data are available for direct analysis of the dose-effect relationships, and extrapolation from high to low doses is still the unavoidable approach in many cases of interest for risk assessment. A review is presented of the data actually available and of the attempts that have been made to obtain possible generalizations. Attention is focused on some specific chromosomal anomalies experimentally induced by radiation (such as reciprocal translocations and aneuploidies in germinal cells) and on their relevance for the human situation. (author)

Dyed grafted films for large-dose radiation dosimetry

Energy Technology Data Exchange (ETDEWEB)

Abdel Rehim, F; El-Sawy, N M; Abdel-Fattah, A A [National Centre for Radiation Research and Technology, Cairo (Egypt)

1993-07-01

By radiation-induced polymerization of acrylic acid onto poly(ethylene-tetrafluoroethylene) (ET) copolymer film and reacting the resulted grafted film with both Rhodamine B (RB) and Malachite Green (MG), new dosimeter films have been developed for high-dose gamma radiation applications in the range of absorbed doses from 10 to 180 kGy. The radiation-induced color bleaching has been analysed with visible spectrophotometry, either at the maximum of the absorption band peaking at 559 nm (for ETRB) or that peaking at 627 nm (for ETMG). The effects of different conditions of absorbed dose rate, temperature and relative humidity during irradiation and post-irradiation storage on dosimeter performance are discussed. (author).

Protective and Therapeutic Role of Low Dose Gamma Radiation on Streptozotocin Induced Diabetes in Rats

International Nuclear Information System (INIS)

Mansour, H.H.; Hafez, H.F.; Shouman, S.A.

2011-01-01

Diabetes mellitus is a multi-factorial disease which is characterized by vascular and renal complication. This study was initiated to investigate the protective and the therapeutic effect of low dose of gamma radiation (LDR) on diabetic complications. A total of 30 adult male rats were divided into 5 groups: Group I: served as control and injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group II: rats became diabetic via intraperitoneal injection with 60 mg/kg streptozotocin (STZ) dissolved in 0.2 ml of 0.1 mol/l citrate buffer (ph 4.5), group III irradiated rats (IRR): submitted to fractionated dose of whole body gamma rays; 0.25 Gy for 2 consecutive days (whole dose 0.5 Gy), group IV diabetic irradiated rats (STZ + IRR): rats became diabetic as group II then four weeks after diabetes induction (day 28), rats were submitted to 2 fractions of whole body gamma rays as in group III, and group V irradiated diabetic rats (IRR + STZ): rats were injected intraperitoneally with 0.2 ml of 0.1 mol/l citrate buffer then submitted to whole body gamma rays; 0.25 Gy for 2 consecutive days then one hour after the last IRR dose, rats were made diabetic as group II. In pre and post-irradiation of STZ rats, significant changes were observed in serum lipid profiles, hepatic and cardiac serum enzymes. Significant decrease in hepatic and cardiac malondialdehyde (MDA) and total nitrate/nitrite (NO(x)) levels, and significant increase in superoxide dismutase (SOD) and glutathione (GSH) levels were observed as compared to diabetic group. The study suggests that LDR may provide useful protective and therapeutic option in the reversal of oxidative stress induced in diabetic rats

Effects of subcutaneous, low-dose glucagon on insulin-induced mild hypoglycaemia in patients with insulin pump treated type 1 diabetes

DEFF Research Database (Denmark)

Ranjan, Ajenthen; Schmidt, S; Madsbad, Sten

2016-01-01

AIM: To investigate the dose-response relationship of subcutaneous glucagon administration on plasma glucose and on counterregulatory hormone responses during subcutaneous insulin induced mild hypoglycaemia in patients with type 1 diabetes treated with insulin pumps. MATERIALS AND METHODS: Eight...... hypoglycaemia in patients with type 1 diabetes....... insulin pump treated patients completed a blinded, randomized, placebo-controlled study. Hypoglycaemia was induced in the fasting state by a subcutaneous insulin bolus and when plasma glucose reached 3.4 mmol/l (95%CI 3.2-3.5), a subcutaneous bolus of either 100, 200, 300 µg glucagon or saline...

Comparison of early treatment with low doses of nilotinib, imatinib and a clinically relevant dose of silymarin in thioacetamide-induced liver fibrosis.

Science.gov (United States)

Shaker, Mohamed E; Shiha, Gamal E; Ibrahim, Tarek M

2011-11-30

Our previous study has already confirmed a promising anti-fibrotic activity especially for nilotinib; when given at a daily dose of 10 mg/kg during the last 4 weeks of thioacetamide (TAA)-induced liver fibrosis for 12 weeks in rats. Therefore, this study was carried out to compare the prophylactic potential of low dose of nilotinib to that of its predecessor, imatinib, and a clinically relevant dose of the standard hepatoprotective treatment, silymarin, in TAA-intoxication. Male Wistar rats received intraperitoneal injections of TAA (150 mg/kg, twice weekly) for 8 weeks, as well as oral treatments with imatinib (5 mg/kg/day), nilotinib (5 mg/kg/day) and silymarin (50 mg/kg/day) from the first day of TAA-intoxication. At the end of the study, chronic hepatic injury was evaluated by analysis of liver function tests in serum. Hepatic oxidative stress was assessed by measuring malondialdehyde, 4-hydroxynonenal, total nitrate/nitrite and reduced glutathione contents, as well as myeloperoxidase and superoxide dismutase activities. Hepatic fibrosis was evaluated by histopathology and collagen content. Our results suggest that the prophylactic potential of nilotinib (5 mg/kg/day), imatinib (5mg/kg/day) and silymarin (50 mg/kg/day) in TAA-intoxication for 8 weeks is lower than the late treatments of nilotinib (10 mg/kg/day), imatinib (10mg/kg/day) and silymarin (100 mg/kg/day) during the last 4 weeks of TAA-intoxication for 12 weeks in rats. Taken together, this study suggests that nilotinib may have higher anti-fibrotic activity when administered at a significant stage of fibrosis as a result of impairment of its metabolism in the fibrotic livers. Copyright © 2011 Elsevier B.V. All rights reserved.

Brief oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis in allogeneic hematopoietic stem cell transplant recipients.

Science.gov (United States)

Mori, Takehiko; Yamazaki, Rie; Aisa, Yoshinobu; Nakazato, Tomonori; Kudo, Masumi; Yashima, Tomoko; Kondo, Sakiko; Ikeda, Yasuo; Okamoto, Shinichiro

2006-04-01

We previously reported the efficacy of oral cryotherapy for the prevention of high-dose melphalan-induced stomatitis. The purpose of this study was to evaluate whether the further shortening of the duration of oral cryotherapy could minimize its side effects while sparing its efficacy. Seventeen consecutive recipients of allogeneic hematopoieic stem cell transplant conditioned with high-dose melphalan in combination with fludarabine alone or with fludarabine and additional radiation were enrolled in the study. The severity of stomatitis was graded according to the National Cancer Institute-Common Toxicity Criteria. Patients were kept on oral cryotherapy shortly before, during, and for additional 30 min after the completion of melphalan administration (60-min oral cryotherapy). Patients who were also enrolled in our previous study received the same type of oral cryotherapy but for additional 90 min after the completion of melphalan administration (120-min oral cryotherapy), and they served as controls. Only 2 (11.8%) of 17 patients receiving 60-min oral cryotherapy and 2 (11.1%) of 18 patients receiving 120-min oral cryotherapy developed grade 2 or 3 stomatitis, respectively. The difference between groups was not statistically significant (P = 0.677). The incidence of unpleasant symptoms such as chills and nausea during oral cryotherapy decreased significantly with 60-min oral cryotherapy, as compared with that associated with 120-min oral cryotherapy (P cryotherapy is as effective as 120-min oral cryotherapy at preventing high-dose melphalan-induced stomatitis, and shorter treatment might have contributed to relieve patient discomfort during oral cryotherapy.

Mutation frequencies in male mice and the estimation of genetic hazards of radiation in men: (specific-locus mutations/dose-rate effect/doubling dose/risk estimation)

International Nuclear Information System (INIS)

Russell, W.L.; Kelly, E.M.

1982-01-01

Estimation of the genetic hazards of ionizing radiation in men is based largely on the frequency of transmitted specific-locus mutations induced in mouse spermatogonial stem cells at low radiation dose rates. The publication of new data on this subject has permitted a fresh review of all the information available. The data continue to show no discrepancy from the interpretation that, although mutation frequency decreases markedly as dose rate is decreased from 90 to 0.8 R/min (1 R = 2.6 X 10 -4 coulombs/kg) there seems to be no further change below 0.8 R/min over the range from that dose rate to 0.0007 R/min. Simple mathematical models are used to compute: (a) a maximum likelihood estimate of the induced mutation frequency at the low dose rates, and (b) a maximum likelihood estimate of the ratio of this to the mutation frequency at high dose rates in the range of 72 to 90 R/min. In the application of these results to the estimation of genetic hazards of radiation in man, the former value can be used to calculate a doubling dose - i.e., the dose of radiation that induces a mutation frequency equal to the spontaneous frequency. The doubling dose based on the low-dose-rate data compiled here is 110 R. The ratio of the mutation frequency at low dose rate to that at high dose rate is useful when it becomes necessary to extrapolate from experimental determinations, or from human data, at high dose rates to the expected risk at low dose rates. The ratio derived from the present analysis is 0.33

Adaptive response of apoptosis in EL-4 lymphoma cells induced by low dose radiation and its mechanism

International Nuclear Information System (INIS)

Liu Shuchun; Gong Pingsheng; Wang Zhicheng; Sun Liguang; Gong Shouliang

2008-01-01

EL-4 lymphoma cells were irradiated with the inductive doses (D1: 25-200 mGy, dose rate: 12.5mGy/min) and the challenging dose (D2:0.5-3.0 Gy, dose rate: 287 mGy/min), and the time interval between D1 and D2 was 6 h. The percentage of cell apoptosis and the expressive levels of cell apoptosis-associated gene pro- reins were measured with flow cytometry. The percentages of cell apoptosis in the D1 + D2 group with 25-100 mGy (D1) and 1.5 Gy (D2) or 75 mGy (D1) and 25-200 mGy (D2) were significantly lower than those in the D2 group. As compared with the D2 group, the positive percentage of cell Bcl-2 protein expression increased somewhat, and Bax decreased significantly, meanwhile the ratio of Bcl-2/Bax increased significantly and p53 decreased somewhat in D1 + D2 group with 25-100 mGy (D1) and 1.5 Gy (D2). The adaptive response of EL-4 lymphoma cell apoptosis could be induced by pre-irradiation with 25-100 mGy. Meantime, the expressive levels of cell apoptosis-associated gene Bcl-2, Bax and p53 proteins could change accordingly with cell apoptosis. These gene protein changes may play an important role in the mechanism of the adaptive response. (authors)

Validating the pivotal role of the immune system in low-dose radiation-induced tumor inhibition in Lewis lung cancer-bearing mice.

Science.gov (United States)

Zhou, Lei; Zhang, Xiaoying; Li, Hui; Niu, Chao; Yu, Dehai; Yang, Guozi; Liang, Xinyue; Wen, Xue; Li, Min; Cui, Jiuwei

2018-04-01

Although low-dose radiation (LDR) possesses the two distinct functions of inducing hormesis and adaptive responses, which result in immune enhancement and tumor inhibition, its clinical applications have not yet been elucidated. The major obstacle that hinders the application of LDR in the clinical setting is that the mechanisms underlying induction of tumor inhibition are unclear, and the risks associated with LDR are still unknown. Thus, to overcome this obstacle and elucidate the mechanisms mediating the antitumor effects of LDR, in this study, we established an in vivo lung cancer model to investigate the participation of the immune system in LDR-induced tumor inhibition and validated the pivotal role of the immune system by impairing immunity with high-dose radiation (HDR) of 1 Gy. Additionally, the LDR-induced adaptive response of the immune system was also observed by sequential HDR treatment in this mouse model. We found that LDR-activated T cells and natural killer cells and increased the cytotoxicity of splenocytes and the infiltration of T cells in the tumor tissues. In contrast, when immune function was impaired by HDR pretreatment, LDR could not induce tumor inhibition. However, when LDR was administered before HDR, the immunity could be protected from impairment, and tumor growth could be inhibited to some extent, indicating the induction of the immune adaptive response by LDR. Therefore, we demonstrated that immune enhancement played a key role in LDR-induced tumor inhibition. These findings emphasized the importance of the immune response in tumor radiotherapy and may help promote the application of LDR as a novel approach in clinical practice. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Effect of low dose rate irradiation on doped silica core optical fibers

International Nuclear Information System (INIS)

Friebele, E.J.; Askins, C.G.; Gingerich, M.E.

1984-01-01

The optical attenuation induced in multimode doped silica core optical fiber waveguides by a year's exposure to low dose rate (1 rad/day) ionizing radiation was studied, allowing a characterization of fibers deployed in these environments and a determination of the permanent induced loss in the waveguides. Variations in the induced attenuation at 0.85 μm have been observed with changes in the dose rate between 1 rad/day and 9000 rads/min. These dose rate dependences have been found to derive directly from the recovery that occurs during the exposure; the recovery data predict little or no dose rate dependence of the damage at 1.3 μm. The low dose rate exposure has been found to induce significant permanent attenuation in the 0.7-1.7-μm spectral region in all fibers containing P in the core, whether doped uniformly across the diameter or constrained to a narrow spike on the centerline. Whereas permanent loss was induced at 0.85 μm in a P-free binary Ge-doped silica core fiber by the year's exposure, virtually no damage was observed at 1.3 μm

CARCINOGENIC EFFECTS OF LOW DOSES OF IONIZING RADIATION

Science.gov (United States)

Carcinogenic Effects of Low Doses of Ionizing RadiationR Julian Preston, Environmental Carcinogenesis Division, NHEERL, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711The form of the dose-response curve for radiation-induced cancers, particu...

Dose-response relationships and risk estimates for the induction of cancer due to low doses of low-LET radiation

International Nuclear Information System (INIS)

Elaguppillai, V.

1981-01-01

Risk estimates for radiation-induced cancer at low doses can be obtained only by extrapolation from the known effects at high doses and high dose rates, using a suitable dose-response model. The applicability of three different models, linear, sublinear and supralinear, are discussed in this paper. Several experimental studies tend to favour a sublinear dose-response model (linear-quadratic model) for low-LET radiation. However, human epidemiological studies do not exclude any of the dose-response relationships. The risk estimates based on linear and linear quadratic dose-response models are compared and it is concluded that, for low-LET radiation, the linear dose-response model would probably over-estimate the actual risk of cancer by a factor of two or more. (author)

Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice

International Nuclear Information System (INIS)

Bestak, Rosa; Halliday, G.M.

1996-01-01

It has previously been demonstrated that chronic low-dose solar-simulated UV radiation could induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. In this study, we have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/HeJ mice. Irradiation with UVA+B significantly suppressed the local and systemic primary contact hypersensitivity (CHS) response to the hapten 2,4,6-trinitrochlorobenzene. Furthermore, UVA+B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) densities in chronically UV-irradiated mice. Ultraviolet A irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with both UVA+B and UVA radiation also induced an impaired secondary CHS response, and this tolerance was transferable with spleen cells. (Author)

Repeated dose intramuscular injection of the CIMAvax-EGF vaccine in Sprague Dawley rats induces local and systemic toxicity.

Science.gov (United States)

Mancebo, A; Casacó, A; González, B; Ledón, N; Sorlozabal, J; León, A; Gómez, D; González, Y; Bada, A M; González, C; Arteaga, M E; Ramírez, H; Fuentes, D

2012-05-09

CIMAvax-EGF consists of a human recombinant epidermal growth factor (EGF), coupled to P64k, a recombinant carrier protein from N. meningitis, and Montanide ISA 51 as adjuvant. The vaccine immunization induces a specific antibody production, inhibiting the EGF/EGF-R interaction through EGF deprivation. The objective of this study was to assess the CIMAvax-EGF toxicity in Sprague Dawley rats after intramuscular administration of repeated doses (6 months) and at the same time to determine if rat is a relevant species for studying CIMAvax-EGF vaccine. Rats were randomly distributed into four groups: control, Montanide ISA 51, treated with 1× and 15× of human total dose of the antigen. Animals were immunized weekly during 9 weeks, plus 9 immunizations every 14 days. Rats were inspected daily for clinical signs. Body weight, food consumption, and rectal temperature were measured during the administration of doses. Blood samples were collected for hematological, serum biochemical determinations and EGF titles at the beginning, three months and at the end of experimentation. Gross necropsy and histological examination of tissues were performed on animals at the end of the assay. Vaccine provoked the apparition of antibodies against EGF in the rats, demonstrating rat species relevance in these studies. Body weight gain, food and water consumption were not affected. CIMAvax-EGF and Montanide ISA 51 produced local damage at the administration site, showing multiple cysts and granulomas. Both vaccine-treated groups showed neutrophil elevation, besides an AST increase probably related to the damage at the administration site. Rectal temperature was found to be significantly higher in 15× treated group after immunizations, probably induced by the inflammatory process at the injection site. In summary, the clinical pathology findings together with the body temperature results, appear to be caused by the inflammatory reaction at the administration site of the vaccine, mainly

Measuring radiation dose to patients undergoing fluoroscopically-guided interventions

International Nuclear Information System (INIS)

Lubis, L E; Badawy, M K

2016-01-01

The increasing prevalence and complexity of fluoroscopically guided interventions (FGI) raises concern regarding radiation dose to patients subjected to the procedure. Despite current evidence showing the risk to patients from the deterministic effects of radiation (e.g. skin burns), radiation induced injuries remain commonplace. This review aims to increase the awareness surrounding radiation dose measurement for patients undergoing FGI. A review of the literature was conducted alongside previous researches from the authors’ department. Studies pertaining to patient dose measurement, its formalism along with current advances and present challenges were reviewed. Current patient monitoring techniques (using available radiation dosimeters), as well as the inadequacy of accepting displayed dose as patient radiation dose is discussed. Furthermore, advances in real-time patient radiation dose estimation during FGI are considered. Patient dosimetry in FGI, particularly in real time, remains an ongoing challenge. The increasing occurrence and sophistication of these procedures calls for further advances in the field of patient radiation dose monitoring. Improved measuring techniques will aid clinicians in better predicting and managing radiation induced injury following FGI, thus improving patient care. (paper)

No adaptive response is induced by chronic low-dose radiation from Ra-226 in the CHSE/F fish embryonic cell line and the HaCaT human epithelial cell line

Energy Technology Data Exchange (ETDEWEB)

Shi, Xiaopei, E-mail: shix22@mcmaster.ca; Mothersill, Carmel; Seymour, Colin

2016-11-15

Purpose: To determine whether chronic low-dose α-particle radiation from Ra-226 over multiple cell generations can lead to an adaptive response in CHSE/F fish embryonic cells or HaCaT human epithelial cells receiving subsequent acute high-dose γ-ray radiation. Methods: CHSE/F and HaCaT cells were exposed to very low doses of Ra-226 in medium for multiple generations prior to being challenged by a higher dose γ-ray radiation. The clonogenic assay was used to test the clonogenic survival of cells with or without being pretreated by radiation from Ra-226. Results: In general, pretreatment with chronic radiation has no significant influence on the reaction of cells to the subsequent challenge radiation. Compared to unprimed cells, the change in clonogenic survival of primed cells after receiving challenge radiation is mainly due to the influence of the chronic exposure, and there's little adaptive response induced. However at several dose points, pretreatment of CHSE/F fish cells with chronic radiation resulted in a radiosensitive response to a challenge dose of γ-ray radiation, and pretreatment of HaCaT cells resulted in no effect except for a slightly radioresistant response to the challenge radiation which was not significant. Conclusion: The results suggest that chronic low-dose radiation is not effective enough to induce adaptive response. There was a difference between human and fish cells and it may be important to consider results from multiple species before making conclusions about effects of chronic or low doses of radiation in the environment. The term “radiosensitive” or “adaptive” make no judgment about whether such responses are ultimately beneficial or harmful. - Highlights: • No obvious adaptive response is induced by chronic low-dose radiation from Ra-226. • Priming radiation from Ra-226 sensitized CHSE/F cells to the challenge radiation. • Linear model is inconsistent with current work using chronic low-dose radiation.

Gamma-irradiated onions as a biological indicator of radiation dose

International Nuclear Information System (INIS)

Vaijapurkar, S.G.; Agarwal, Deepshikha; Chaudhuri, S.K.; Ram Senwar, Kana; Bhatnagar, P.K.

2001-01-01

Post-irradiation identification and dose estimation are required to assess the radiation-induced effects on living things in any nuclear emergency. In this study, radiation-induced morphological/cytological changes i.e., number of root formation and its length, shooting length, reduction in mitotic index, micronuclei formation and chromosomal aberrations in the root tip cells of gamma-irradiated onions at lower doses (50-2000 cGy) are reported. The capabilities of this biological species to store the radiation-induced information are also studied

Sci-Thur AM: YIS – 02: Imaging dose distributions through the detection of radiation-induced acoustic waves

Energy Technology Data Exchange (ETDEWEB)

Hickling, Susannah; Lei, Hao; Hobson, Maritza; Leger, Pierre; Wang, Xueding; El Naqa, Issam [University of Michigan, McGill University, McGill University , University of Michigan, University of Michigan/McGill University (United States)

2016-08-15

Purpose: X-ray acoustic computed tomography (XACT) is an emerging technique that images the dose deposited within an object following linac irradiation by detecting acoustic waves induced via the photoacoustic effect. This work shows that XACT images can be formed in soft-tissue equivalent material and that dosimetric information can be extracted from such images. Methods: Acoustic waves induced in a water tank following irradiation by a 10 MV flattening filter free photon beam were detected with an immersion ultrasound transducer at 60 angles surrounding the radiation field. A back-projection algorithm was used to reconstruct an XACT image from the detected transducer signals. Profiles extracted from XACT images were compared to profiles measured with ion chambers as per the current clinical protocol. Results: XACT images were successfully formed of simple 4 cm × 4 cm and 6 cm × 3 cm fields, as well as of more complicated multi-leaf collimator defined fields. For the 6 cm × 3 cm field, 74% and 87% of the XACT profile points in the 6 cm and 3 cm dimensions, respectively, passed a 7% / 4 mm gamma test when compared to ion chamber measurements. In a complicated puzzle piece shaped field, 86% of the pixels in an extracted profile passed a 7% / 4 mm gamma test. Conclusions: XACT is capable of imaging the dose distribution delivered by a variety of field sizes and shapes in water, and is a viable technique for both water tank and in vivo dosimetry.

Toxicogenomic analysis of the particle dose- and size-response relationship of silica particles-induced toxicity in mice

International Nuclear Information System (INIS)

Lu Xiaoyan; Jin Tingting; Jin Yachao; Wu Leihong; Hu Bin; Tian Yu; Fan Xiaohui

2013-01-01

This study investigated the relationship between particle size and toxicity of silica particles (SP) with diameters of 30, 70, and 300 nm, which is essential to the safe design and application of SP. Data obtained from histopathological examinations suggested that SP of these sizes can all induce acute inflammation in the liver. In vivo imaging showed that intravenously administrated SP are mainly present in the liver, spleen and intestinal tract. Interestingly, in gene expression analysis, the cellular response pathways activated in the liver are predominantly conserved independently of particle dose when the same size SP are administered or are conserved independently of particle size, surface area and particle number when nano- or submicro-sized SP are administered at their toxic doses. Meanwhile, integrated analysis of transcriptomics, previous metabonomics and conventional toxicological results support the view that SP can result in inflammatory and oxidative stress, generate mitochondrial dysfunction, and eventually cause hepatocyte necrosis by neutrophil-mediated liver injury. (paper)

Hand-foot syndrome in a patient with metastatic lung adenocarcinoma induced by high-dose icotinib: A case report and review of the literature

OpenAIRE

ZHENG, YULONG; FANG, WEIJIA; XU, NONG

2012-01-01

Icotinib is a new oral epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI). The most frequent side-effects of icotinib include rash and diarrhea. Hand-foot syndrome (HFS) induced by EGFR-TKI is rare. The present study describes, for the first time, HFS induced by high-dose icotinib in a 65-year old female with metastatic lung adenocarcinoma. The patient developed HFS during the first week of icotinib treatment with characteristic clinical presentation. HFS regressed after icotinib do...

Effects of subanesthetic doses of ketamine in cats with induced experimental endotoxemia

Directory of Open Access Journals (Sweden)

Felipe Hertzing Farias

2015-12-01

Full Text Available ABSTRACT. Farias F.H., Gehrcke M.I., Padilha V.S., Volpato J., Tochetto R., Comassetto F. & Oleskovicz N. [Effects of subanesthetic doses of ketamine in cats with induced experimental endotoxemia.] Efeitos da cetamina em doses subanestésicas em gatos submetidos à endotoxemia experimental. Revista Brasileira de Medicina Veterinária, 37(4:297-302, 2015. Programa de Pós-Graduação em Ciência Animal, Centro de Ciências Agroveterinárias, Universidade do Estado de Santa Catarina, Avenida Luís de Camões, 2090, Bairro Conta Dinheiro, Lages, SC 88520-000, Brasil. E-mail: noleskovicz@yahoo.com.br The clinical endotoxemia is difficult to diagnosis and treatment because of the involvement of multiple organs. This study aimed to evaluate the clinical effects of subanesthetic doses of ketamine, before or after the induction of endotoxemia in cats. Were used nine healthy cats, with 4.3±0.59 kg, autocontroles, placed into three groups: lipopolysaccharide (LPS, n=9 received a bolus of NaCl 0,9 % followed by a continuous infusion (CI of LPS for two hours and; bolus of NaCl 0,9 % followed by CI of LPS for two hours; ketamine/LPS (C/ LPS, n=9 received a bolus of ketamine followed by ketamine CI and LPS for two hours and, after, bolus of saline followed by CI of LPS for another two hours; LPS/ketamine (LPS/C, n=9 received bolus of saline followed by a CI LPS for two hours and then after bolus of ketamine followed by the same CI associated with LPS for two hours. The heart rate was higher for 5 to 120 minutes after initiation of the CI LPS in C/LPS and less than 150 to 240 minutes and from 600 to 720 minutes in LPS compared to the other groups. Five minutes after CI LPS initiation in C/LPS, 60 minutes in LPS/C and 90 minutes to 720 minutes in LPS, FC was higher than at baseline. The PAS was lower in all groups from 360 to 720 minutes compared to baseline. All treatments showed increased TR from 60 to 600 minutes compared to baseline. The levels of glucose

Health effect of low dose/low dose rate radiation

International Nuclear Information System (INIS)

Kodama, Seiji

2012-01-01

The clarified and non-clarified scientific knowledge is discussed to consider the cause of confusion of explanation of the title subject. The low dose is defined roughly lower than 200 mGy and low dose rate, 0.05 mGy/min. The health effect is evaluated from 2 aspects of clinical symptom/radiation hazard protection. In the clinical aspect, the effect is classified in physical (early and late) and genetic ones, and is classified in stochastic (no threshold value, TV) and deterministic (with TV) ones from the radioprotection aspect. Although the absence of TV in the carcinogenic and genetic effects has not been proved, ICRP employs the stochastic standpoint from the safety aspect for radioprotection. The lowest human TV known now is 100 mGy, meaning that human deterministic effect would not be generated below this dose. Genetic deterministic effect can be observable only in animal experiments. These facts suggest that the practical risk of exposure to <100 mGy in human is the carcinogenesis. The relationship between carcinogenic risk in A-bomb survivors and their exposed dose are found fitted to the linear no TV model, but the epidemiologic data, because of restriction of subject number analyzed, do not always mean that the model is applicable even below the dose <100 mGy. This would be one of confusing causes in explanation: no carcinogenic risk at <100 mGy or risk linear to dose even at <100 mGy, neither of which is scientifically conclusive at present. Also mentioned is the scarce risk of cancer in residents living in the high background radiation regions in the world in comparison with that in the A-bomb survivors exposed to the chronic or acute low dose/dose rate. Molecular events are explained for the low-dose radiation-induced DNA damage and its repair, gene mutation and chromosome aberration, hypothesis of carcinogenesis by mutation, and non-targeting effect of radiation (bystander effect and gene instability). Further researches to elucidate the low dose

Analgesia induced by repeated exposure to low dose X-rays in mice, and involvement of the accessory olfactory system in modulation of the radiation effects

International Nuclear Information System (INIS)

Miyachi, Yukihisa; Yamada, Takeshi

1997-01-01

The effects of low-dose X-rays on mouse nociceptive behavior were examined using a formalin injected test which rated the amount of time the animals spent licking the injected hind-paw. Male ICR White Swiss mice showed a marked suppression of licking behavior after repeated low-dose X-irradiation (5 cGy/day, 6 consecutive days). The most profound effect was observed on the day 30 after irradiation. The decline of licking behavior, however, was not observed at all following olfactory bulbectomy or vomeronasal tract cut. The analgesic effects could be observed in writhing animals administered acetic-acid intraperitoneally. Moreover, analgesia was totally blocked by the administration of N-nitro-L-arginine, a nitric oxide synthase inhibitor, to accessory olfactory bulbs prior to the exposure. The present results indicate that the olfactory system plays an important role in modulation of radiation-induced analgesia, and a possible involvement of nitric oxide in the formation of recognition memory subjected to repeated X-rays. Relatively higher doses (5 cGy x 9 days, 5 cGy x 12 days), however, did not induce such effects, namely, the decline of nociceptive response was limited to the animals irradiated with the smaller dose. (author)

Dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells of mice

Science.gov (United States)

Luo, Lan; Yan, Chen; Urata, Yoshishige; Hasan, Al Shaimaa; Goto, Shinji; Guo, Chang-Ying; Zhang, Shouhua; Li, Tao-Sheng

2017-01-01

We evaluated the dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells (CDCs), a mixed cell population grown from heart tissues. Adult C57BL/6 mice were exposed to 0, 10, 50 and 250 mGy γ-rays for 7 days and atrial tissues were collected for experiments 24 hours after last exposure. The number of CDCs was significantly decreased by daily exposure to over 250 mGy. Interestingly, daily exposure to over 50 mGy significantly decreased the c-kit expression and telomerase activity, increased 53BP1 foci in the nuclei of CDCs. However, CD90 expression and growth factors production in CDCs were not significantly changed even after daily exposure to 250 mGy. We further evaluated the reversibility of radiation-induced injury in CDCs at 1 week and 3 weeks after a single exposure to 3 Gy γ-rays. The number and growth factors production of CDCs were soon recovered at 1 week. However, the increased expression of CD90 were retained at 1 week, but recovered at 3 weeks. Moreover, the decreased expression of c-kit, impaired telomerase activity, and increased 53BP1 foci were poorly recovered even at 3 weeks. These data may help us to find the most sensitive and reliable bio-parameter(s) for evaluating radiation-induced injury in CDCs. PMID:28098222

Patient radiation doses from neuroradiology procedures

Energy Technology Data Exchange (ETDEWEB)

Garcia-Roman, M J; Abreu-Luis, J; Hernandez-Armas, J [Servicio de Fisica Medica, Hospital Universitario de Canarias, La Laguna, Tenerife (Spain); Prada-Martinez, E [Servicio de Radiodiagnostico, Hospital Universitario de Canarias, La Laguna, Tenerife (Spain)

2001-03-01

Following the presentation of radiation-induced deterministic effects by some patients undergoing neuroradiological procedures during successive sessions, such as temporary epilation, in the 'Hospital Universitario de Canarias', measurements were made of dose to patients. The maximum dose-area product measured by ionization chamber during these procedures was 39617 cGy.cm{sup 2} in a diagnostic of aneurysm and the maximum dose to the skin measured by thermoluminescent dosemeters (TLDs) was 462.53 mGy. This can justify certain deterministic effects but it is unlikely that the patients will suffer serious effects from this skin dose. Also, measurements were made of effective dose about two usual procedures, embolisation of tumour und embolisation of aneurysm. These procedures were reproduced with an anthropomorphic phantom Rando and doses were measured with TLDs. Effective doses obtained were 3.79 mSv and 4.11 mSv, respectively. The effective dose valued by the program EFFDOSE was less than values measured with TLDs. (author)

Patient radiation doses from neuroradiology procedures

International Nuclear Information System (INIS)

Garcia-Roman, M.J.; Abreu-Luis, J.; Hernandez-Armas, J.; Prada-Martinez, E.

2001-01-01

Following the presentation of radiation-induced deterministic effects by some patients undergoing neuroradiological procedures during successive sessions, such as temporary epilation, in the 'Hospital Universitario de Canarias', measurements were made of dose to patients. The maximum dose-area product measured by ionization chamber during these procedures was 39617 cGy.cm 2 in a diagnostic of aneurysm and the maximum dose to the skin measured by thermoluminescent dosemeters (TLDs) was 462.53 mGy. This can justify certain deterministic effects but it is unlikely that the patients will suffer serious effects from this skin dose. Also, measurements were made of effective dose about two usual procedures, embolisation of tumour und embolisation of aneurysm. These procedures were reproduced with an anthropomorphic phantom Rando and doses were measured with TLDs. Effective doses obtained were 3.79 mSv and 4.11 mSv, respectively. The effective dose valued by the program EFFDOSE was less than values measured with TLDs. (author)

Fast motion-including dose error reconstruction for VMAT with and without MLC tracking

DEFF Research Database (Denmark)

Ravkilde, Thomas; Keall, Paul J.; Grau, Cai

2014-01-01

of the algorithm for reconstruction of dose and motion-induced dose errors throughout the tracking and non-tracking beam deliveries was quantified. Doses were reconstructed with a mean dose difference relative to the measurements of -0.5% (5.5% standard deviation) for cumulative dose. More importantly, the root...... validate a simple model for fast motion-including dose error reconstruction applicable to intrafractional QA of MLC tracking treatments of moving targets. MLC tracking experiments were performed on a standard linear accelerator with prototype MLC tracking software guided by an electromagnetic transponder......-mean-square deviation between reconstructed and measured motion-induced 3%/3 mm γ failure rates (dose error) was 2.6%. The mean computation time for each calculation of dose and dose error was 295 ms. The motion-including dose reconstruction allows accurate temporal and spatial pinpointing of errors in absorbed dose...

ER signaling is activated to protect human HaCaT keratinocytes from ER stress induced by environmental doses of UVB

International Nuclear Information System (INIS)

Mera, Kentaro; Kawahara, Ko-ichi; Tada, Ko-ichi; Kawai, Kazuhiro; Hashiguchi, Teruto; Maruyama, Ikuro; Kanekura, Takuro

2010-01-01

Proteins are folded properly in the endoplasmic reticulum (ER). Various stress such as hypoxia, ischemia and starvation interfere with the ER function, causing ER stress, which is defined by the accumulation of unfolded protein (UP) in the ER. ER stress is prevented by the UP response (UPR) and ER-associated degradation (ERAD). These signaling pathways are activated by three major ER molecules, ATF6, IRE-1 and PERK. Using HaCaT cells, we investigated ER signaling in human keratinocytes irradiated by environmental doses of ultraviolet B (UVB). The expression of Ero1-Lα, an upstream signaling molecule of ER stress, decreased at 1-4 h after 10 mJ/cm 2 irradiation, indicating that the environmental dose of UVB-induced ER stress in HaCaT cells, without growth retardation. Furthermore, expression of intact ATF6 was decreased and it was translocated to the nuclei. The expression of XBP-1, a downstream molecule of IRE-1, which is an ER chaperone whose expression is regulated by XBP-1, and UP ubiquitination were induced by 10 mJ/cm 2 UVB at 4 h. PERK, which regulates apoptosis, was not phosphorylated. Our results demonstrate that UVB irradiation generates UP in HaCaT cells and that the UPR and ERAD systems are activated to protect cells from UVB-induced ER stress. This is the first report to show ER signaling in UVB-irradiated keratinocytes.

Watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice modulates oxidative damage induced by low dose X-ray in mice.

Science.gov (United States)

Mohammad, Mohd Khairul Amran; Mohamed, Muhamad Idham; Zakaria, Ainul Mardhiyah; Abdul Razak, Hairil Rashmizal; Saad, Wan Mazlina Md

2014-01-01

Watermelon is a natural product that contains high level of antioxidants and may prevent oxidative damage in tissues due to free radical generation following an exposure to ionizing radiation. The present study aimed to investigate the radioprotective effects of watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice against oxidative damage induced by low dose X-ray exposure in mice. Twelve adult male ICR mice were randomly divided into two groups consisting of radiation (Rx) and supplementation (Tx) groups. Rx received filtered tap water, while Tx was supplemented with 50% (v/v) watermelon juice for 28 days ad libitum prior to total body irradiation by 100 μGy X-ray on day 29. Brain, lung, and liver tissues were assessed for the levels of malondialdehyde (MDA), apurinic/apyrimidinic (AP) sites, glutathione (GSH), and superoxide dismutase (SOD) inhibition activities. Results showed significant reduction of MDA levels and AP sites formation of Tx compared to Rx (P watermelon juice restore the intracellular antioxidant activities by significantly increased SOD inhibition activities and GSH levels compared to Rx. These findings may postulate that supplementation of 50% watermelon (Citrullus lanatus (Thunb.) Matsum. and Nakai) juice could modulate oxidative damage induced by low dose X-ray exposure.

Effect of low dose radiation on apoptosis in mouse spleen

International Nuclear Information System (INIS)

Chen Dong; Liu Jiamei; Chen Aijun; Liu Shuzheng

1999-01-01

Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis

Dose response relationships and analysis of primary processes of radiation-induced chromosomal aberrations in human peripheral lymphocytes

International Nuclear Information System (INIS)

Schmid, E.

1977-02-01

Human peripheral lymphocytes were irradiated with 220 kV X-rays, 3 MeV electrons and 15 MeV neutrons. The frequency of dicentric, acentric and atypical chromosomes and the exhange aberrations were measured and dose effect curves were constructed. The aim is to prepare the chromosome analysis to a biological dosimetry. The aberration findings could be adapted to the linear-quadrativ model y = c+ αD + βD 2 . With increasing LET the quantity lambda increased which is a measure for the share of the linear and quadratical components of the dose effect obtained. In case of electrons the RBE-values increased with increasing doses. In the case of neutrons they had their maximum in the low dose range. The feed back distances which lead to formation of primary lesions are for X-rays and electrons approximately 1 μm, for neutrons 1.7 μm. In a fractionation experiment with X-rays, the time of formation of exchange aberrations in radiation-induced primary breaks was measured. The number of dicentric chromosomes decreased with increasing time, while the intercellular distribution was not changed. The number of primary breaks decreasing per temporal interval is proportional to the number of the existing primary breaks. The average feed back time during which the primary breaks lead to induction of dicentric chromosomes, is 110 min. In order to determine the correspondence of the results of in-vivo and in-vitro experiments 15 patients and their blood were irradiated with 60 C-γ-rays. No significant differences were measured. (AJ) [de

Low dose diagnostic radiation does not increase cancer risk in cancer prone mice

Energy Technology Data Exchange (ETDEWEB)

Boreham, D., E-mail: dboreham@nosm.ca [Northern Ontario School of Medicine, ON (Canada); Phan, N., E-mail: nghiphan13@yahoo.com [Univ. of Ottawa, Ottawa, ON (Canada); Lemon, J., E-mail: lemonja@mcmaster.ca [McMaster Univ., Hamilton, ON (Canada)

2014-07-01

The increased exposure of patients to low dose diagnostic ionizing radiation has created concern that these procedures will result in greater risk of carcinogenesis. However, there is substantial evidence that shows in many cases that low dose exposure has the opposite effect. We have investigated whether CT scans can modify mechanisms associated with carcinogenesis in cancer-prone mice. Cancer was induced in Trp53+/- mice with an acute high dose whole-body 4 Gy γ-radiation exposure. Four weeks following the cancer-inducing dose, weekly whole-body CT scans (10 mGy/scan, 75 kVp X-rays) were given for ten consecutive weeks adding an additional radiation burden of 0.1 Gy. Short-term biological responses and subsequent lifetime cancer risk were investigated. Five days following the last CT scan, there were no detectable differences in the spontaneous levels of DNA damage in blood cells (reticulocytes). In fact, CT scanned mice had significantly lower constitutive levels of oxidative DNA damage and cell death (apoptosis), compared to non-CT scanned mice. This shows that multiple low dose radiation exposures modified the radio response and indicates protective processes were induced in mice. In mice treated with the multiple CT scans following the high cancer-inducing 4 Gy dose, tumour latency was increased, significantly prolonging lifespan. We conclude that repeated CT scans can reduce the cancer risk of a prior high-dose radiation exposure, and delay the progression of specific types of radiation-induced cancers in Trp53+/-mice. This research shows for the first time that low dose exposure long after cancer initiation events alter risk and reduce cancer morbidity. Cancer induction following low doses does not follow a linear non-threshold model of risk and this model should not be used to extrapolate risk to humans following low dose exposure to ionizing radiation. (author)

Induction of IgG memory responses with polyvinylpyrrolidone (PVP) is antigen dose dependent

International Nuclear Information System (INIS)

Lite, H.S.; Braley-Mullen, H.

1981-01-01

Irradiated recipients of spleen cells from mice primed with a very low dose (0.0025 μ/g) of the thymus-independent (TI) antigen polyvinylpyrrolidone (PVP) produced PVP-specific IgG memory responses after secondary challenge with a T-dependent (TD) form of PVP, PVP-HRBC. The IgG memory responses induced by low doses of PVP were similar in magnitude to those induced by the TD antigen PVP-HRBC. The induction of IgG memory by the TI form of antigen was markedly dependent on the dose of PVP used to prime donor mice. Spleen cells from mice primed with an amount of PVP (0.25 μg) that induces an optimal primary IgM response did not produce significant IgG antibody after challenge with PVP-HRBC. The inability of higher doses of PVP to induce IgG memory may be due, at least in part, to the fact that such doses of PVP were found to induce tolerance in PVP-specific B cells and could suppress the induction of memory induced by PVP-HRBC. Low doses of PVP did not interfere with the induction of memory by PVP-HRBC. Expression of IgG memory responses in recipients of PVP-HRBC or low-dose PVP-primed cells was found to be T cell dependent. Moreover, only primed T cells could reconstitute the respnse of recipients of primed B cells, suggesting that the ability of PVP to induce IgG memory may be related to its ability to prime T helper cells. Expression of the IgG memory response in recipient mice also required the use of a TD antigen for secondary challenge, i.e., mice challenged with PVP did not develop IgG

Effects of dose, dose-rate and fraction on radiation-induced breast and lung cancers

International Nuclear Information System (INIS)

Howe, G.R.

1992-01-01

Recent results from a large Canadian epidemiologic cohort study of low-LET radiation and cancer will be described. This is a study of 64,172 tuberculosis patients first treated in Canada between 1930 and 1952, of whom many received substantial doses to breast and lung tissue from repeated chest fluoroscopies. The mortality of the cohort between 1950 and 1987 has been determined by computerized record linkage to the National Mortality Data Base. There is a strong positive association between radiation and breast cancer risk among the females in the cohort, but in contrast very little evidence of any increased risk in lung cancer. The results of this and other studies suggest that the effect of dose-rate and/or fractionation on cancer risk may will differ depending upon the particular cancer being considered. (author)

Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia

Directory of Open Access Journals (Sweden)

Balaji Ramachandran

Full Text Available EGCG (Epigallocatechin-3-gallate is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal] and limited [p.o (oral] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment. Keywords: EGCG, Green tea, Serum lipids, Dose dependant toxicity, Route dependant toxicity, Liver toxicity, Dyslipidemia

Study of genomic instability induced by low dose ionizing radiation

International Nuclear Information System (INIS)

Seoane, A.; Crudeli, C.; Dulout, F.

2006-01-01

The crews of commercial flights and services staff of radiology and radiotherapy from hospitals are exposed to low doses of ionizing radiation. Genomic instability includes those adverse effects observed in cells, several generations after the exposure occurred. The purpose of this study was to analyze the occurrence of genomic instability by very low doses of ionizing radiation [es

Low-dose tryptophan depletion in recovered depressed women induces impairments in autobiographical memory specificity.

Science.gov (United States)

Haddad, Anneke D M; Williams, J Mark G; McTavish, Sarah F B; Harmer, Catherine J

2009-12-01

Depressed patients perform poorly on tests of autobiographical memory specificity (AMS); this may have negative consequences for other important cognitive abilities, delays recovery from mood episodes, and, in recovered patients, may mediate vulnerability to future episodes. Although the cognitive mechanisms underlying AMS deficits are beginning to be understood, the neurobiological mechanisms remain unclear. Serotonin is implicated in both depression and long-term memory; therefore, temporary lowering of brain serotonin function via acute tryptophan depletion (ATD) offers a means of studying the role of serotonin in autobiographical memory specificity. In this study, 24 previously depressed women underwent low-dose ATD or sham depletion and completed tests of initial and delayed memory, recollection- and familiarity-based recognition, and AMS. ATD did not differentially affect state mood. Compared with sham depletion, ATD impaired immediate recall on the Auditory Verbal Learning Test. Although ATD did not differentially impair recollection- and familiarity-based recognition, it did slow recognition of positive words. ATD also reduced autobiographical memory specificity in response to negative cue words. The results confirm previous findings that low-dose ATD can reinstate depression-congruent biases in cognition without causing depressive mood in vulnerable populations. The ATD-induced reduction in memory specificity suggests that serotonergic dysfunction may mediate depressive deficits in autobiographical memory; the interaction of cognitive and neurobiological vulnerability mechanisms is discussed.

Establishment and verification of dose-response curve of chromosomal aberrations after exposure to very high dose γ-ray

International Nuclear Information System (INIS)

Chen Ying; Luo Yisheng; Cao Zhenshan; Liu Xiulin

2006-01-01

To estimate accurately biological dose of the victims exposed to high dose, the dose-response curves of chromosome aberration induced by 6-22 Gy 60 Co γ-ray were established. Human peripheral blood in vitro was irradiated, then lymphocytes were concentrated, cultured 52h, 68h and 72h and harvested. The frequencies of dicentrics (multi-centrics) and rings were counted and compared between different culture times. The dose-response curves and equations were established, as well as verified with high dose exposure accidents. The experiment showed that the culture time should be prolonged properly after high dose exposure, and no significant differences were observed between 52-72h culture. The dose-response curve of 6-22 Gy fitted to linear-square model Y=-2.269 + 0.776D - 7.868 x 10 -3 D 2 and is reliable through verification of the accident dose estimations. In this study, the dose-response curve and equation of chromosome dic + r after 6-22 Gy high dose irradiation were established firstly, and exact dose estimation can be achieved according to it. (authors)

Management of pediatric radiation dose using Philips fluoroscopy systems DoseWise: perfect image, perfect sense

International Nuclear Information System (INIS)

Stueve, Dick

2006-01-01

Although image quality (IQ) is the ultimate goal for accurate diagnosis and treatment, minimizing radiation dose is equally important. This is especially true when pediatric patients are examined, because their sensitivity to radiation-induced cancer is two to three times greater than that of adults. DoseWise is an ALARA-based philosophy within Philips Medical Systems that is active at every level of product design. It encompasses a set of techniques, programs and practices that ensures optimal IQ while protecting people in the X-ray environments. DoseWise methods include management of the X-ray beam, less radiation-on time and more dose information for the operator. Smart beam management provides automatic customization of the X-ray beam spectrum, shape, and pulse frequency. The Philips-patented grid-controlled fluoroscopy (GCF) provides grid switching of the X-ray beam in the X-ray tube instead of the traditional generator switching method. In the examination of pediatric patients, DoseWise technology has been scientifically documented to reduce radiation dose to <10% of the dose of traditional continuous fluoroscopy systems. The result is improved IQ at a significantly lower effective dose, which contributes to the safety of patients and staff. (orig.)

DNA–PKcs–SIN1 complexation mediates low-dose X-ray irradiation (LDI)-induced Akt activation and osteoblast differentiation

Energy Technology Data Exchange (ETDEWEB)

Xu, Yong; Fang, Shi-ji [The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000 (China); Zhu, Li-juan [Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and Institute of Neuroscience, Soochow University, Suzhou, Jiangsu 215021 (China); Zhu, Lun-qing, E-mail: xiaodongwangsz@163.com [The Center of Diagnosis and Treatment for Children’s Bone Diseases, The Children’s Hospital Affiliated to Soochow University, Suzhou, Jiangsu 215000 (China); Zhou, Xiao-zhong, E-mail: zhouxz@suda.edu.cn [The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000 (China)

2014-10-24

Highlights: • LDI increases ALP activity, promotes type I collagen (Col I)/Runx2 mRNA expression. • LDI induces DNA–PKcs activation, which is required for osteoblast differentiation. • Akt activation mediates LDI-induced ALP activity and Col I/Runx2 mRNA increase. • DNA–PKcs–SIN1 complexation mediates LDI-induced Akt Ser-473 phosphorylation. • DNA–PKcs–SIN1 complexation is important for osteoblast differentiation. - Abstract: Low-dose irradiation (LDI) induces osteoblast differentiation, however the underlying mechanisms are not fully understood. In this study, we explored the potential role of DNA-dependent protein kinase catalytic subunit (DNA–PKcs)–Akt signaling in LDI-induced osteoblast differentiation. We confirmed that LDI promoted mouse calvarial osteoblast differentiation, which was detected by increased alkaline phosphatase (ALP) activity as well as mRNA expression of type I collagen (Col I) and runt-related transcription factor 2 (Runx2). In mouse osteoblasts, LDI (1 Gy) induced phosphorylation of DNA–PKcs and Akt (mainly at Ser-473). The kinase inhibitors against DNA–PKcs (NU-7026 and NU-7441) or Akt (LY294002, perifosine and MK-2206), as well as partial depletion of DNA–PKcs or Akt1 by targeted-shRNA, dramatically inhibited LDI-induced Akt activation and mouse osteoblast differentiation. Further, siRNA-knockdown of SIN1, a key component of mTOR complex 2 (mTORC2), also inhibited LDI-induced Akt Ser-473 phosphorylation as well as ALP activity increase and Col I/Runx2 expression in mouse osteoblasts. Co-immunoprecipitation (Co-IP) assay results demonstrated that LDI-induced DNA–PKcs–SIN1 complexation, which was inhibited by NU-7441 or SIN1 siRNA-knockdown in mouse osteoblasts. In summary, our data suggest that DNA–PKcs–SIN1 complexation-mediated Akt activation (Ser-473 phosphorylation) is required for mouse osteoblast differentiation.

A comparison of radiation dose to the neurovascular bundles in men with and without prostate brachytherapy-induced erectile dysfunction

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Dorsey, Anthony T.; Lief, Jonathan H.; Donzella, Joseph G.

2000-01-01

thresholds and side of the gland. The dose distribution over the length of the prostate rose smoothly from the base and apex to peak at midgland in 125 I implants while 103 Pd implants had a relatively constant dose over the length of the prostate. Considering the calculation grid as forming a 6-mm wide ribbon along each side of the prostate, the average patient had 70 mm 2 area receiving at least 300% of mPD. Conclusion: In this study, no relationship between radiation dose to the NVB and the development of post brachytherapy erectile dysfunction was discernible. Such a difference may become evident with additional follow-up. If long-term brachytherapy-induced erectile dysfunction is related to the radiation dose to the NVB, the ultimate preservation of potency following prostate brachytherapy may be markedly inferior to what has been reported. Nevertheless, the majority of this patient population responded favorably to sildenafil

Transplacental exposure to inorganic arsenic at a hepatocarcinogenic dose induces fetal gene expression changes in mice indicative of aberrant estrogen signaling and disrupted steroid metabolism

International Nuclear Information System (INIS)

Liu Jie; Xie Yaxiong; Cooper, Ryan; Ducharme, Danica M.K.; Tennant, Raymond; Diwan, Bhalchandra A.; Waalkes, Michael P.

2007-01-01

Exposure to inorganic arsenic in utero in C3H mice produces hepatocellular carcinoma in male offspring when they reach adulthood. To help define the molecular events associated with the fetal onset of arsenic hepatocarcinogenesis, pregnant C3H mice were given drinking water containing 0 (control) or 85 ppm arsenic from day 8 to 18 of gestation. At the end of the arsenic exposure period, male fetal livers were removed and RNA isolated for microarray analysis using 22K oligo chips. Arsenic exposure in utero produced significant (p < 0.001) alterations in expression of 187 genes, with approximately 25% of aberrantly expressed genes related to either estrogen signaling or steroid metabolism. Real-time RT-PCR on selected genes confirmed these changes. Various genes controlled by estrogen, including X-inactive-specific transcript, anterior gradient-2, trefoil factor-1, CRP-ductin, ghrelin, and small proline-rich protein-2A, were dramatically over-expressed. Estrogen-regulated genes including cytokeratin 1-19 and Cyp2a4 were over-expressed, although Cyp3a25 was suppressed. Several genes involved with steroid metabolism also showed remarkable expression changes, including increased expression of 17β-hydroxysteroid dehydrogenase-7 (HSD17β7; involved in estradiol production) and decreased expression of HSD17β5 (involved in testosterone production). The expression of key genes important in methionine metabolism, such as methionine adenosyltransferase-1a, betaine-homocysteine methyltransferase and thioether S-methyltransferase, were suppressed. Thus, exposure of mouse fetus to inorganic arsenic during a critical period in development significantly alters the expression of various genes encoding estrogen signaling and steroid or methionine metabolism. These alterations could disrupt genetic programming at the very early life stage, which could impact tumor formation much later in adulthood

Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

Science.gov (United States)

Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

2016-01-01

EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

Intranasal administration of a therapeutic HIV vaccine (Vacc-4x induces dose-dependent systemic and mucosal immune responses in a randomized controlled trial.

Directory of Open Access Journals (Sweden)

Kristin Brekke

Full Text Available Vacc-4x, a Gag p24-based therapeutic HIV vaccine, has been shown to reduce viral load set-points after intradermal administration. In this randomized controlled pilot study we investigate intranasal administration of Vacc-4x with Endocine as adjuvant.Safety and immunogenicity were tested in patients on effective ART. They were randomized to low, medium or high dose Vacc-4x or adjuvant alone, administered four times at weekly intervals with no booster. Vacc-4x-specific T cell responses were measured in vitro by proliferation and in vivo by a single DTH skin test at the end of study. Nasal and rectal mucosal secretions were analyzed for Vacc-4x-specific antibodies by ELISA. Immune regulation induced by Vacc-4x was assessed by functional blockade of the regulatory cytokines IL-10 and TGF-β.Vacc-4x proliferative T cell responses increased only among the vaccinated (p ≤ 0.031. The low dose group showed the greatest increase in Vacc-4x CD8+T cell responses (p = 0.037 and developed larger DTH (p = 0.005 than the adjuvant group. Rectal (distal Vacc-4x IgA and IgG antibodies also increased (p = 0.043 in this group. In contrast, the high dose generated higher nasal (local Vacc-4x IgA (p = 0.028 and serum IgG (p = 0.030 antibodies than the adjuvant. Irrespective of dose, increased Vacc-4x CD4+T cell responses were associated with low proliferation (r = -0.82, p < 0.001 and high regulation (r = 0.61, p = 0.010 at baseline.Intranasal administration of Vacc-4x with Endocine was safe and induced dose-dependent vaccine-specific T cell responses and both mucosal and systemic humoral responses. The clinical significance of dose, immune regulation and mucosal immunity warrants further investigation.ClinicalTrials.gov NCT01473810.

Cytogenetic effect of low dose gamma-radiation in Hordeum vulgare seedlings: non-linear dose-effect relationship.

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Geras'kin, Stanislav A; Oudalova, Alla A; Kim, Jin Kyu; Dikarev, Vladimir G; Dikareva, Nina S

2007-03-01

The induction of chromosome aberrations in Hordeum vulgare germinated seeds was studied after ionizing irradiation with doses in the range of 10-1,000 mGy. The relationship between the frequency of aberrant cells and the absorbed dose was found to be nonlinear. A dose-independent plateau in the dose range from about 50 to 500 mGy was observed, where the level of cytogenetic damage was significantly different from the spontaneous level. The comparison of the goodness of the experimental data fitting with mathematical models of different complexity, using the most common quantitative criteria, demonstrated the advantage of a piecewise linear model over linear and polynomial models in approximating the frequency of cytogenetical disturbances. The results of the study support the hypothesis of indirect mechanisms of mutagenesis induced by low doses. Fundamental and applied implications of these findings are discussed.

Chronic Low Dose Rate Ionizing Radiation Exposure Induces Premature Senescence in Human Fibroblasts that Correlates with Up Regulation of Proteins Involved in Protection against Oxidative Stress

Directory of Open Access Journals (Sweden)

Olga Loseva

2014-07-01

Full Text Available The risks of non-cancerous diseases associated with exposure to low doses of radiation are at present not validated by epidemiological data, and pose a great challenge to the scientific community of radiation protection research. Here, we show that premature senescence is induced in human fibroblasts when exposed to chronic low dose rate (LDR exposure (5 or 15 mGy/h of gamma rays from a 137Cs source. Using a proteomic approach we determined differentially expressed proteins in cells after chronic LDR radiation compared to control cells. We identified numerous proteins involved in protection against oxidative stress, suggesting that these pathways protect against premature senescence. In order to further study the role of oxidative stress for radiation induced premature senescence, we also used human fibroblasts, isolated from a patient with a congenital deficiency in glutathione synthetase (GS. We found that these GS deficient cells entered premature senescence after a significantly shorter time of chronic LDR exposure as compared to the GS proficient cells. In conclusion, we show that chronic LDR exposure induces premature senescence in human fibroblasts, and propose that a stress induced increase in reactive oxygen species (ROS is mechanistically involved.

Radiation-induced heart disease due to intrathonacic tumor radiotherapy of a single dose to the rabbits' heart

International Nuclear Information System (INIS)

Zhou Weibing; Feng Yan; Chen Jiayi; Luo Quanyong

2007-01-01

Objective: To observe the changes of radiation-induced heart disease (RIHD) in the rabbits irradiated in clinical related dose, and to evaluate the apoptosis and hypoxia in the irradiated heart by the new scintigraphic agents of 99 Tc m -HL91 and 99 Tc m -Annexin V of heart SPECT. Methods: Tenty-four New Zealand white rabbits 4-month old and 2-3 kg by weight were divided into two groups. Group 1 (clinical related dose group): 16 irradiated by a single close from 0 to 18 Gy. Group 2 (high dose group): 8 irradiated dose from 22 to 80 Gy. The serum cTnI/CKMB, ECG, and heart SPECT(using 99 Tc m -MIBI, 99 Tc m -HL91 and 99 Tc m -Annexin V as agents) were detected before and after irradiation. The animals were followed for 5 months. Then biopsy of rabbit heart was performed and pathologic examination was made by H.E. stain. Results: In the 16 rabbits of clinical related dose group, none died of RIHD. Whereas 2 rabbits died of RIHD in the high dose group. One died of myocardial infarction and the other of congestive heart failure. According to the Stewart introduced heart lesion grading system, of the clinical close ann, there were moderate in 1 rabbit, minimal in 14; and of the high dose ann, it was severe in 2, marked in 1, moderate in 5. The parallel relation was observed between the ECG results and the pathological changes (χ 2 =0.08, P=0.771). Serum value of cTnI, was elevated at the 12th hour after irradiation reaching the peak and maintained for 4 months. However, it came down in the 5th month. The difference of serum cTnI value before and after radiation was statistically significant. Myocardial perfusion scintigraphy tested by heart SPECT ( 99 Tc m -MIBI) showed defects was present in all irradiated rabbits. The relationship between the defects and radiation dose or between the defects and the real RIHD was uncertain. The SPECT images displayed that 99 Tc m -HL91 and 99m Tc-Annexin V did not accumulate in the irradiated heart. Conclusions: No serious damage is

Radiation sources providing increased UVA/UVB ratios induce photoprotection dependent on the UVA dose in hairless mice.

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Reeve, Vivienne E; Domanski, Diane; Slater, Michael

2006-01-01

In studies involving mice in which doses of UVA (320-400 nm) and UVB (290-320 nm) radiation were administered alone or combined sequentially, we observed a protective effect of UVA against UVB-induced erythema/edema and systemic suppression of contact hypersensitivity. The UVA immunoprotection was mediated by the induction of the stress enzyme heme oxygenase-1 (HO-1) in the skin, protection of the cutaneous Th1 cytokines interferon-gamma (IFN-gamma) and IL-12 and inhibition of the UVB-induced expression of the Th2 cytokine IL-10. In this study, we seek evidence for an immunological waveband interaction when UVA and UVB are administered concurrently to hairless mice as occurs during sunlight exposure in humans. A series of spectra providing varying ratios of UVA/UVB were developed, with the UVA ratio increased to approximately 3.5 times the UVA component in solar simulated UV (SSUV). We report that progressively increasing the UVA component of the radiation while maintaining a constant UVB dose resulted in a reduction of both the erythema/edema reaction and the degree of systemic immunosuppression, as measured as contact hypersensitivity. The UVA-enhanced immunoprotection was abrogated in mice treated with a specific HO enzyme inhibitor. UVA-enhanced radiation also upregulated the expression of cutaneous IFN-gamma and IL-12 and inhibited expression of both IL-6 and IL-10, compared with the activity of SSUV. The results were consistent with the previously characterized mechanisms of photoprotection by the UVA waveband alone and suggest that the UVA component of solar UV may have beneficial properties for humans.

Superfractionation as a potential hypoxic cell radiosensitizer: prediction of an optimum dose per fraction

International Nuclear Information System (INIS)

Dasu, Alexandru; Denekamp, Juliana

1999-01-01

Purpose: A dose 'window of opportunity' has been identified in an earlier modeling study if the inducible repair variant of the LQ model is adopted instead of the pure LQ model, and if all survival curve parameters are equally modified by the presence or absence of oxygen. In this paper we have extended the calculations to consider survival curve parameters from 15 sets of data obtained for cells tested at low doses using clonogenic assays. Methods and Materials: A simple computer model has been used to simulate the response of each cell line to various doses per fraction in multifraction schedules, with oxic and hypoxic cells receiving the same fractional dose. We have then used pairs of simulated survival curves to estimate the effective hypoxic protection (OER') as a function of the dose per fraction. Results: The resistance of hypoxic cells is reduced by using smaller doses per fraction than 2 Gy in all these fractionated clinical simulations, whether using a simple LQ model, or the more complex LQ/IR model. If there is no inducible repair, the optimum dose is infinitely low. If there is inducible repair, there is an optimum dose per fraction at which hypoxic protection is minimized. This is usually around 0.5 Gy. It depends on the dose needed to induce repair being higher in hypoxia than in oxygen. The OER' may even go below unity, i.e. hypoxic cells may be more sensitive than oxic cells. Conclusions: If oxic and hypoxic cells are repeatedly exposed to doses of the same magnitude, as occurs in clinical radiotherapy, the observed hypoxic protection varies with the fractional dose. The OER' is predicted to diminish at lower doses in all cell lines. The loss of hypoxic resistance with superfractionation is predicted to be proportional to the capacity of the cells to induce repair, i.e. their intrinsic radioresistance at a dose of 2 Gy

Dose and dose rate effects of whole-body gamma-irradiation: II. Hematological variables and cytokines

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Gridley, D. S.; Pecaut, M. J.; Miller, G. M.; Moyers, M. F.; Nelson, G. A.

2001-01-01

The goal of part II of this study was to evaluate the effects of gamma-radiation on circulating blood cells, functional characteristics of splenocytes, and cytokine expression after whole-body irradiation at varying total doses and at low- and high-dose-rates (LDR, HDR). Young adult C57BL/6 mice (n = 75) were irradiated with either 1 cGy/min or 80 cGy/min photons from a 60Co source to cumulative doses of 0.5, 1.5, and 3.0 Gy. The animals were euthanized at 4 days post-exposure for in vitro assays. Significant dose- (but not dose-rate-) dependent decreases were observed in erythrocyte and blood leukocyte counts, hemoglobin, hematocrit, lipopolysaccharide (LPS)-induced 3H-thymidine incorporation, and interleukin-2 (IL-2) secretion by activated spleen cells when compared to sham-irradiated controls (p factor-beta 1 (TGF-beta 1) and splenocyte secretion of tumor necrosis factor-alpha (TNF-alpha) were not affected by either the dose or dose rate of radiation. The data demonstrate that the responses of blood and spleen were largely dependent upon the total dose of radiation employed and that an 80-fold difference in the dose rate was not a significant factor in the great majority of measurements.

We can do better than effective dose for estimating or comparing low-dose radiation risks

International Nuclear Information System (INIS)

Brenner, D.J.

2012-01-01

The effective dose concept was designed to compare the generic risks of exposure to different radiation fields. More commonly these days, it is used to estimate or compare radiation-induced cancer risks. For various reasons, effective dose represents flawed science: for instance, the tissue-specific weighting factors used to calculate effective dose are a subjective mix of different endpoints; and the marked and differing age and gender dependencies for different health detriment endpoints are not taken into account. This paper suggests that effective dose could be replaced with a new quantity, ‘effective risk’, which, like effective dose, is a weighted sum of equivalent doses to different tissues. Unlike effective dose, where the tissue-dependent weighting factors are a set of generic, subjective committee-defined numbers, the weighting factors for effective risk are simply evaluated tissue-specific lifetime cancer risks per unit equivalent dose. Effective risk, which has the potential to be age and gender specific if desired, would perform the same comparative role as effective dose, be just as easy to estimate, be less prone to misuse, be more directly understandable, and would be based on solid science. An added major advantage is that it gives the users some feel for the actual numerical values of the radiation risks they are trying to control.

Evaluation of the potential inhibitor of Ix (Pp-Ix) protoporphyrin of the genetic damage induced by gamma rays administered to different dose reasons in Drosophila melanogaster

International Nuclear Information System (INIS)

Flores A, J. A.

2016-01-01

Ionizing radiation can damage in DNA directly or indirectly by free radicals (Rl), characterized by unstable and highly reactive. To avoid damage by Rl the cell has endogenous antioxidants such as Sod, Cat, GSH or exogenous as some vitamins, but if with these mechanisms does not reach the cell homeostasis, the consequence may be the generation of chronic-disease degenerative such as cancer. This study was conducted in order to test the inhibitory role of Rl protoporphyrin Ix (Pp-Ix), induced by 20 Gy of gamma rays administered at different dose ratios using the assay of somatic mutation and recombination in the Drosophila wing. The results indicated that 20 Gy delivered at a rate of low dose (6.659 Gy/h), caused elevated frequencies of genetic damage (p <0.001), compared with those that induced a high dose reason (1111.42 Gy/h) in larvae of 48 h old. The difference is probably due to an indirect damage by Rl; when this hypothesis was approved with the possible inhibitor role of Pp-Ix (0.69 m M), damage was increased with the two reasons of tested doses. This result may be due to: 1) the Pp-Ix is not a good inhibitor of Rl, 2) the difference in the frequency of mutation found with both dose reasons, not due to Rl so that this compound did not reduce the genetic damage, and 3) that Pp-Ix acts as pro oxidant. (Author)

Comparison of ketorolac and low-dose ketamine in preventing tourniquet-induced increase in arterial pressure

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Raza Zaidi

2015-01-01

Full Text Available Background and Aims: Application of tourniquet during orthopaedic procedures causes pain and increase in blood pressure despite adequate anaesthesia and analgesia. In this study, we compared ketorolac with ketamine in patients undergoing elective lower limb surgery with tourniquet in order to discover if ketorolac was equally effective or better than ketamine in preventing tourniquet-induced hypertension. Methods: Approval was granted by the Institutional Ethics Review Committee and informed consent was obtained from all participants. A randomised double-blinded controlled trial with 38 patients each in the ketamine and ketorolac groups undergoing elective knee surgery for anterior cruciate ligament repair or reconstruction was conducted. Induction and maintenance of anaesthesia were standardised in all patients, and the minimum alveolar concentration of isoflurane was maintained at 1.2 throughout the study period. One group received ketamine in a dose of 0.25 mg/kg and the other group received 30 mg ketorolac 10 min before tourniquet inflation. Blood pressure was recorded before induction of anaesthesia (baseline and at 0, 10, 20, 30, 40, 50, and 60 min after tourniquet inflation. Results: The demographic and anaesthetic characteristics were similar in the two groups. At 0 and 10 min, tourniquet-induced rise in blood pressure was not observed in both groups. From 20 min onward, both systolic and diastolic blood pressures were significantly higher in ketorolac group compared to ketamine group. Conclusion: We conclude that ketamine is superior to ketorolac in preventing tourniquet-induced increases in blood pressure.

Expression of a Human Cytochrome P450 in Yeast Permits Analysis of Pathways for Response to and Repair of Aflatoxin-Induced DNA Damage†

OpenAIRE

Guo, Yingying; Breeden, Linda L.; Zarbl, Helmut; Preston, Bradley D.; Eaton, David L.

2005-01-01

Aflatoxin B1 (AFB1) is a human hepatotoxin and hepatocarcinogen produced by the mold Aspergillus flavus. In humans, AFB1 is primarily bioactivated by cytochrome P450 1A2 (CYP1A2) and 3A4 to a genotoxic epoxide that forms N7-guanine DNA adducts. A series of yeast haploid mutants defective in DNA repair and cell cycle checkpoints were transformed with human CYP1A2 to investigate how these DNA adducts are repaired. Cell survival and mutagenesis following aflatoxin B1 treatment was assayed in str...

Experimental ultraviolet photocarcinogenesis: wavelength interactions and time-dose relationships.

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Forbes, P D; Davies, R E; Urbach, F

1978-12-01

Tumors were induced in the skin of SKH hairless mice by exposure to fluorescent FS sun lamps or to a long-arc xenon solar simulator. Tumores developed about equally well with varying amounts of UV-A radiation (lambda greater than 320 nm) given simultaneously. In contrast, incremental changes in the UV-B region (lambda less than 320 nm) led to substantial increases in carcinogenic effectiveness. A tumor-"initiating" dose of UV-B (4-10 wk of daily FS lamp exposures) was rendered less effective by subsequent exposures of the mice to UV-A (6 hr/day, F-40 T12BL lamps). The mechanism for this effect is not known. Most tumors induced by a short course (10 wk) of FS lamp exposure grew slowly or regressed, whereas mice exposed for a longer period (30 wk) developed more tumors, and many of those that appeared early grew aggressively. Effects of daily dose fractionation were less clear, and the subject requires further study. These and other variables are being tested in a program designed to yield useful information on the effects of changing spectrum, dose, and dose delivery rates on sunlight-induced cancer.

SU-F-J-86: Method to Include Tissue Dose Response Effect in Deformable Image Registration

Energy Technology Data Exchange (ETDEWEB)

Zhu, J; Liang, J; Chen, S; Qin, A; Yan, D [Beaumont Health Systeml, Royal Oak, MI (United States)

2016-06-15

Purpose: Organ changes shape and size during radiation treatment due to both mechanical stress and radiation dose response. However, the dose response induced deformation has not been considered in conventional deformable image registration (DIR). A novel DIR approach is proposed to include both tissue elasticity and radiation dose induced organ deformation. Methods: Assuming that organ sub-volume shrinkage was proportional to the radiation dose induced cell killing/absorption, the dose induced organ volume change was simulated applying virtual temperature on each sub-volume. Hence, both stress and heterogeneity temperature induced organ deformation. Thermal stress finite element method with organ surface boundary condition was used to solve deformation. Initial boundary correspondence on organ surface was created from conventional DIR. Boundary condition was updated by an iterative optimization scheme to minimize elastic deformation energy. The registration was validated on a numerical phantom. Treatment dose was constructed applying both the conventional DIR and the proposed method using daily CBCT image obtained from HN treatment. Results: Phantom study showed 2.7% maximal discrepancy with respect to the actual displacement. Compared with conventional DIR, subvolume displacement difference in a right parotid had the mean±SD (Min, Max) to be 1.1±0.9(−0.4∼4.8), −0.1±0.9(−2.9∼2.4) and −0.1±0.9(−3.4∼1.9)mm in RL/PA/SI directions respectively. Mean parotid dose and V30 constructed including the dose response induced shrinkage were 6.3% and 12.0% higher than those from the conventional DIR. Conclusion: Heterogeneous dose distribution in normal organ causes non-uniform sub-volume shrinkage. Sub-volume in high dose region has a larger shrinkage than the one in low dose region, therefore causing more sub-volumes to move into the high dose area during the treatment course. This leads to an unfavorable dose-volume relationship for the normal organ

Two doses of bovine viral diarrhea virus DNA vaccine delivered by electroporation induce long-term protective immune responses.

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van Drunen Littel-van den Hurk, Sylvia; Lawman, Zoe; Snider, Marlene; Wilson, Don; van den Hurk, Jan V; Ellefsen, Barry; Hannaman, Drew

2013-02-01

Bovine viral diarrhea virus (BVDV) is a pathogen of major importance in cattle, so there is a need for new effective vaccines. DNA vaccines induce balanced immune responses and are relatively inexpensive and thus promising for both human and veterinary applications. In this study, newborn calves with maternal antibodies were vaccinated intramuscularly (i.m.) with a BVDV E2 DNA vaccine with the TriGrid Delivery System for i.m. delivery (TDS-IM). Two doses of this vaccine spaced 6 or 12 weeks apart were sufficient to induce significant virus-neutralizing antibody titers, numbers of activated T cells, and reduction in viral shedding and clinical presentations after BVDV-2 challenge. In contrast to the placebo-treated animals, the vaccinated calves did not lose any weight, which is an excellent indicator of the well-being of an animal and has a significant economic impact. Furthermore, the interval between the two vaccinations did not influence the magnitude of the immune responses or degree of clinical protection, and a third immunization was not necessary or beneficial. Since electroporation may enhance not only the magnitude but also the duration of immunity after DNA immunization, the interval between vaccination and challenge was extended in a second trial, which showed that two doses of this E2 DNA vaccine again significantly reduced clinical disease against BVDV for several months. These results are promising and support this technology for use against infectious diseases in cattle and large species, including humans, in general.

Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior

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Leclercq, Sophie; Mian, Firoz M.; Stanisz, Andrew M.; Bindels, Laure B.; Cambier, Emmanuel; Ben-Amram, Hila; Koren, Omry; Forsythe, Paul; Bienenstock, John

2017-01-01

There is increasing concern about potential long-term effects of antibiotics on children's health. Epidemiological studies have revealed that early-life antibiotic exposure can increase the risk of developing immune and metabolic diseases, and rodent studies have shown that administration of high doses of antibiotics has long-term effects on brain neurochemistry and behaviour. Here we investigate whether low-dose penicillin in late pregnancy and early postnatal life induces long-term effects in the offspring of mice. We find that penicillin has lasting effects in both sexes on gut microbiota, increases cytokine expression in frontal cortex, modifies blood–brain barrier integrity and alters behaviour. The antibiotic-treated mice exhibit impaired anxiety-like and social behaviours, and display aggression. Concurrent supplementation with Lactobacillus rhamnosus JB-1 prevents some of these alterations. These results warrant further studies on the potential role of early-life antibiotic use in the development of neuropsychiatric disorders, and the possible attenuation of these by beneficial bacteria. PMID:28375200

Biological impact of high-dose and dose-rate radiation exposure

International Nuclear Information System (INIS)

Maliev, V.; Popov, D.; Jones, J.; Gonda, S.; Prasad, K.; Viliam, C.; Haase, G.; Kirchin, V.; Rachael, C.

2006-01-01

radiation, a time after radiation, individual and situational conditions of the irradiated object and the environment. A group of essential radiation toxins with antigenic properties expressed significantly and specifically for different forms of the radiation disease represents the group of compounds: glycoproteins and lipoproteins that accumulate in the lymphatic system of mammals at once in the first hours after radiation. The molecular weight of radiation toxins of S.D.R. group constitutes 200-250 k DA. The essential radiation toxins, preparations of S.D.R. (Specific Radiation Determinant), were isolated from the lymphatic system of laboratory and agricultural animals that were irradiated by doses capable to induce development of cerebral (S.D.R. - 1), toxic (S.D.R.-2), gastrointestinal (S.D.R.-3) and typical (S.D.R.-4) forms of the acute radiation disease. Biological properties and reproduction effects of preparations of essential radiation toxins of S.D.R. group depended on a magnitude of radiation doses that animal-donors absorbed being irradiated. The essential radiation toxins of S.D.R. group isolated from the lymphatic system of irradiated animals and injected by the different doses to intact animals can provide the effects which induce development of different forms of the acute radiation disease. Different doses of active biological substance of S.D.R. can provide different effects:1. Optimal doses are necessary for an active immune response and radioprotection effects 2. Toxic doses can induce and stimulate the radiation disease. Optimal doses of S.D.R. preparations applied for active immunization are determined very individually and depend on species of laboratory animals, their weight and gender. Toxic doses of S.D.R. preparations can cause, stimulate and imitate the development of different forms of the acute radiation syndromes and any consequences of the acute radiation disorder. Previously researchers allow making assumption what toxic doses of biological

Biological impact of high-dose and dose-rate radiation exposure

Energy Technology Data Exchange (ETDEWEB)

Maliev, V.; Popov, D. [Russian Academy of Science, Vladicaucas (Russian Federation); Jones, J.; Gonda, S. [NASA -Johnson Space Center, Houston (United States); Prasad, K.; Viliam, C.; Haase, G. [Antioxida nt Research Institute, Premier Micronutrient Corporation, Novato (United States); Kirchin, V. [Moscow State Veterinary and Biotechnology Acade my, Moscow (Russian Federation); Rachael, C. [University Space Research Association, Colorado (United States)

2006-07-01

radiation, a time after radiation, individual and situational conditions of the irradiated object and the environment. A group of essential radiation toxins with antigenic properties expressed significantly and specifically for different forms of the radiation disease represents the group of compounds: glycoproteins and lipoproteins that accumulate in the lymphatic system of mammals at once in the first hours after radiation. The molecular weight of radiation toxins of S.D.R. group constitutes 200-250 k DA. The essential radiation toxins, preparations of S.D.R. (Specific Radiation Determinant), were isolated from the lymphatic system of laboratory and agricultural animals that were irradiated by doses capable to induce development of cerebral (S.D.R. - 1), toxic (S.D.R.-2), gastrointestinal (S.D.R.-3) and typical (S.D.R.-4) forms of the acute radiation disease. Biological properties and reproduction effects of preparations of essential radiation toxins of S.D.R. group depended on a magnitude of radiation doses that animal-donors absorbed being irradiated. The essential radiation toxins of S.D.R. group isolated from the lymphatic system of irradiated animals and injected by the different doses to intact animals can provide the effects which induce development of different forms of the acute radiation disease. Different doses of active biological substance of S.D.R. can provide different effects:1. Optimal doses are necessary for an active immune response and radioprotection effects 2. Toxic doses can induce and stimulate the radiation disease. Optimal doses of S.D.R. preparations applied for active immunization are determined very individually and depend on species of laboratory animals, their weight and gender. Toxic doses of S.D.R. preparations can cause, stimulate and imitate the development of different forms of the acute radiation syndromes and any consequences of the acute radiation disorder. Previously researchers allow making assumption what toxic doses of biological

Agmatine attenuates methamphetamine-induced hyperlocomotion and stereotyped behavior in mice.

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Kitanaka, Nobue; Kitanaka, Junichi; Hall, F Scott; Uhl, George R; Watabe, Kaname; Kubo, Hitoshi; Takahashi, Hitoshi; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Takemura, Motohiko

2014-04-01

We investigated whether pretreatment with the neurotransmitter/neuromodulator agmatine (decarboxylated L-arginine) affected methamphetamine (METH)-induced hyperlocomotion and stereotypy in male ICR mice. Agmatine pretreatment alone had no effects on locomotion or stereotypy, but it produced a dose-dependent attenuation of locomotion and the total incidence of stereotyped behavior induced by a low dose of METH (5 mg/kg). The stereotypy induced by this dose was predominantly characterized by stereotyped sniffing. By contrast, agmatine did not affect the total incidence of stereotypy induced by a higher dose of METH (10 mg/kg). However, the nature of stereotypy induced by this dose of METH was substantially altered; agmatine pretreatment significantly reduced stereotyped biting but significantly increased stereotyped sniffing and persistent locomotion. Agmatine pretreatment therefore appears to produce a rightward shift in the dose-response curve for METH. Pretreatment of mice with piperazine-1-carboxamidine (a putative agmatinase inhibitor) had no effect on locomotion or stereotypy induced by a low dose of METH, suggesting that endogenous agmatine may not regulate the METH action.

Dosimetric systems of high dose, dose rate and dose uniformity in food and medical products

International Nuclear Information System (INIS)

Vargas, J.; Vivanco, M.; Castro, E.

2014-08-01

implants with a weight of 1393 g the maximum dose rate of 6.5276 kGy /h, the minimum dose rate of 3.5684 kGy /h and the dose uniformity of 1 83 were determined. Then, based on the minimum dose rate irradiation times were calculated for different doses to evaluate in the microbial decontamination of food (3, 5, 8 and 12 kGy) and the sterilization of medical material by radiation (15, 20, 25 and 40 kGy), corroborating the applied doses with routine dosimeters of ethanol chlorobenzene (1-100 kGy) and perspex network 4034 (5-50 kGy). Other routine dosimeters used in different applications according to the doses range are Gafchromic Hd (40-400 Gray) for induced mutation by radiation and the development of new varieties of plants, the sterile insect technique to eradicate pests, quarantine treatment to solve plant health problems. Ambar Perspex 3042 C (3-15 kGy) for microbial decontamination of dried foods, spices, aromatic herbs, medicinal plants, etc. GEX B-3000 (1-140 kGy) and FWT (0.5-200 kGy) for sterilization of medical and pharmaceutical material, cosmetics, biological tissues, etc. The minimum dose rate allowing to calculate the irradiation times to apply the desired dose for the research or industrial processes, taking into account the density and geometry of product. Is notorious the difference in dose uniformity in food (1, 16) and medical material (1, 83) due to the geometry and relative density of the products within the irradiation cylinder. (author)

Estimation of population doses from diagnostic medical examinations in Japan, 1974. III. Per caput mean marrow dose and leukemia significant dose

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Hashizume, T; Maruyama, T; Kumamoto, Y [National Inst. of Radiological Sciences, Chiba (Japan)

1976-03-01

The mean per capita marrow dose and leukemia-significant dose from radiographic and fluoroscopic examinations in Japan have been estimated based on a 1974 nation wide survey of randomly sampled hospitals and clinics. To determine the mean marrow dose to an individual from a certain exposure of a given type of examination, the active marrow in the whole body was divided into 119 parts for an adult and 103 for a child. Dosimetric points on which the individual marrow doses were determined were set up in the center of each marrow part. The individual marrow doses at the dosimetric points in the beams of practical diagnostic x-rays were calculated on the basis of the exposure data on the patients selected in the nation wide survey, using depth dose curves experimentally determined for diagnostic x-rays. The mean individual marrow dose was averaged over the active marrow by summing, for each dosimetric point, the product of the fraction of active marrow exposed and the individual marrow dose at the dosimetric point. The leukemia significant dose was calculated by adopting a weighting factor that is, a leukemia significant factor. The factor was determined from the shape of the time-incidence curve for radiation-induced leukemia from the Hiroshima A-bomb and from the survival statistics for the average population. The resultant mean per capita marrow dose from radiographic and fluoroscopic examination was 37.0 and 70.0 mrad/person/year, respectively, with a total of 107.05 mrad/person/year. The leukemia significant dose was 32.1 mrad/person/year for radiographic examination and 61.2 mrad/person/year, with a total of 93.3. These values were compared with those of 1960 and 1969.

Tourniquet-induced ischaemia-reperfusion injury: the comparison of antioxidative effects of small-dose propofol and ketamine

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Karaca Omer

Full Text Available Abstract Objectives: The aim of the present study was to investigate the preventive effects of propofol and ketamine as small dose sedation during spinal anaesthesia on tourniquet-induced ischaemia-reperfusion injury. Methods: 30 patients were randomly assigned into two groups of 15 patients. In the propofol group, sedation was performed with propofol 0.2 mg·kg-1 followed by infusion at a rate of 2 mg·kg-1·h-1. In the ketamine group, a continuous infusion of ketamine 0.5 mg·kg-1·h-1 was used until the end of surgery. Intravenous administration of midazolam was not used in any patients. Ramsay sedation scale was used for assessing the sedation level. Venous blood samples were obtained before propofol and ketamine infusion (T1, at 30 minutes (min of tourniquet ischaemia (T2, and 5 min after tourniquet deflation (T3 for malondialdehyde (MDA measurements. Results: No differences were noted between the groups in haemodynamic (p > 0.05 and demographic data (p > 0.05. There was no statistically significant difference between the two groups in terms of T1, T2 and T3 periods (p > 0.05. There was a statistically increase observed in MDA values respectively both in Group P and Group K between the reperfusion period (1.95 ± 0.59, 2.31 ± 0.48 and pre-ischaemia (1.41 ± 0.38, 1.54 ± 0.45, and ischaemia (1.76 ± 0.70, 1.71 ± 0.38 (µmoL-1 periods (p < 0.05. Conclusions: Small-dose propofol and ketamine has similar potential to reduce the oxidative stress caused by tourniquet-induced ischaemia-reperfusion injury in patients undergoing arthroscopic knee surgery under spinal anaesthesia.

Patient dose and risk in mammography

International Nuclear Information System (INIS)

Law, J.

1991-01-01

Patient dose in mammography is estimated by two methods compared and giving agreement. A mean tissue dose of about 1 mGy per film is found for a breast of 4.5 cm compressed thickness. Variables affecting dose are then considered quantitatively, including compressed breast thickness, tube potential, grids, magnification and beam collimation. The variables having the greatest effect are breast thickness and magnification. The dose estimates are combined with existing data on breast cancer induction to predict the risk of carcinogenesis in a breast screening programme. For example, in a screening centre performing 15 000 examinations per year, only one induced cancer is predicted in about 7 years of screening under average UK conditions of age and breast thickness. (author)