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International Nuclear Information System (INIS)

Carcinogenesis is now generally recognized to be an important detrimental effect in man after low dose irradiation. The carcinogenic action of ionizing radiation is clearly demonstrated after exposure to relatively high doses (in excess of 0.5 Gy) but for lower dose levels reliable direct observations are not available. With the introduction of special protocols for the performance of large scale screening programs by mammography the average absorbed dose in glandular tissue in the average breast can be restricted to a value of 3 mGy per mammogram. The risk for tumor induction after exposure to these low doses can never be established from human epidemiology. In order to investigate the risk of repeated exposure to small dose of ionizing radiation the induction of mammary tumors has been investigated in rats of the WAG/Rij strain after single and fractionated irradiations with gamma-rays. (author). 8 refs., 3 figs.

British Library Electronic Table of Contents (United Kingdom)

The mechanisms underlying the pathogenesis of estrogen-induced breast carcinogenesis remain unclear. The present study investigated the roles of estrogen metabolism and oxidative stress in estrogen-mediated mammary carcinogenesis in vivo. Female August Copenhagen Irish (ACI) rats were treated with 17b-estradiol (E2), the antioxidant vitamin C, the estrogen metabolic inhibitor a-naphthoflavone (ANF), or cotreated with E2 + vitamin C or E2 + ANF for up to 8 months. E2 (3 mg) was administered as an subcutaneous implant, ANF was given via diet (0.2%) and vitamin C (1%) was added to drinking water. At necropsy, breast tumor incidence in the E2, E2 + vitamin C and E2 + ANF groups was 82, 29 and 0%, respectively. Vitamin C and ANF attenuated E2-induced alterations in oxidative stress markers in b...

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No abstract prepared.

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Breast cancer progression is characterized by inappropriate cell growth. Normal cells cease growth after a limited number of cell divisions--a process called cellular senescence-while tumor cells may acquire the ability to proliferate indefinitely (immortality). Inappropriate expression of specific oncogenes in a key cellular signaling pathway (Ras, Raf) can promote tumorigenicity in immortal cells, while causing finite lifespan cells to undergo a rapid senescence-like arrest. We have studied when in the course of transformation of cultured human mammary epithelial cells (HMEC), the response to overexpressed oncogenic Raf changes from being tumor-suppressive to tumor enhancing, and what are the molecular underpinnings of this response. Our data indicate: (1) HMEC acquire the ability to maintain growth in the presence of oncogenic Raf not simply as a consequence of overcoming senescence, but as a result of a newly discovered step in the process of immortal ...

Science.gov (United States)

The Molecular Genetics and Carcinogenesis Section conducts studies using human epithelial cells to assess: activation of proto-oncogenes by chemical and physical carcinogens; inactivation and dysregulation of tumor suppressor genes by chemical and physical

Science.gov (United States)

... Extracellular Signaling through the Microenvironment: A Hypothesis Relating Carcinogenesis, Bystander Effects, and Genomic InstabilityMary Helen Barcellos-Hoff1a ... ...

UK PubMed Central (United Kingdom)

Cancer, by definition, is a proliferative disease. The fundamental scientific issue explored at the international symposium "Cell Proliferation and Chemical Carcinogenesis" was the impact of chemically...Full Text Available

International Nuclear Information System (INIS)

The late effects of "2"3"9Pu have been studied after its administration to perinatal, juvenile and adult rats. Adults and weanlings were injected intravenously, newborns intracardially and 19-day foetuses by intravenous injection of the dam. Dose levels were selected to deliver radiation doses of approximately 7, 23, or 70 rads to the femur of all ages during the first 10 days post injection; in general these values were achieved as shown by tissue analysis. Dose rates subsequently diverged, resulting in widely varying cumulative radiation doses for the four age groups. Survival times of rats exposed post-natally were progressively decreased by increasing dose. No decrement in survival was found for those exposed prenatally. Bone tumour incidence was increased by exposure to Pu in all age groups. The younger rats were less sensitive on an administered dose basis, but perhaps more sensitive on the basis of cumulative radiation dose. Prenatally exposed animals, which were cross-fostered ...

UK PubMed Central (United Kingdom)

Most breast cancers are multicentric in origin. They drain into two primary lymphatic depots—the axilla and internal mammary chain of nodes. The incidence of metastasis to the internal mammary...Full Text Available

UK PubMed Central (United Kingdom)

A total of 262 strains of Staphylococcus aureus isolated from the mammary gland of dairy cows were examined for the production of alpha-hemolysin. Strains were cultured in a liquid medium of casein...Full Text Available

UK PubMed Central (United Kingdom)

We have studied the functions of the intracellular RNAs of mouse mammary tumor virus (MMTV) by purification and translation in vitro. Two major size classes of MMTV RNA, 35S and 24S RNA, were isolated...Full Text Available

UK PubMed Central (United Kingdom)

The cyclic AMP content of acini, freshly prepared from mammary tissue of lactating rats, was measured during incubation in vitro. Neither adrenergic agonists nor cyclic AMP phosphodiesterase inhibitors...Full Text Available

Science.gov (United States)

... Loss of Heterozygosity in Normal Breast Epithelial Tissue and Benign Breast Lesions in BRCA1/2 Carriers with Breast Cancer. ...

Science.gov (United States)

We report for the first time a relationship between the Tpl-2/cot oncogene and Mouse Mammary Tumor Virus (MMTV) associated transformation of mammary gland cells. A sub-genomic library generated from a primary mammary gland tumor yielded a novel MMTV integration site which disrupted the Tpl-2/cot proto-oncogene between exons 7 and 8. Comparison of a cell line derived from normal mammary gland (comma-D) and a cell line established from an MMTV induced mammary tumor (GR) demonstrated similar rearrangements within Tpl-2/cot for the GR cells but not in the comma-D cells. These rearrangements in the cell line were accompanied by an increase in the level of Tpl-2/cot specific mRNA. This data suggests that Tpl-2/cot expression may be important in epithelial cell transformation or tumor progression. PMID:8934549

UK PubMed Central (United Kingdom)

Objectives. The inescapable relationship between chronic inflammation and carcinogenesis has long been established. Our objective was to investigate COX-2 and NF-κB...Full Text Available

International Nuclear Information System (INIS)

The presence of washed or unwashed cellophane alone or together with a bleomycin, mitomycin C or hydrochlorothiazide, ('Esidrex') showed no appreciable effect on survival of either unirradiated or irradiated conidia. Irradiation for a period of 20min reduced the survival of conidia to 20%. The growth of irradiated conidia in the presence of bleomycin, mitomycin C or Esidrex is associated with a 2- to 3-fold increase in the frequency of gene convertants, but was not accompanied by an increase in point mutants. When conidia were grown on cellophane but otherwise treated as before the frequency of gene convertants was increased 8-fold, but induction of point mutants was negligible. This effect was the same for irradiated and unirradiated conidia. The environment created by the cellophane in contract with the medium appears to affect the action of each of the three compounds synergistically. (author).

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We have observed significant differences in the response to ionizing radiation of two closely related human cell lines, and now compare the effects on these lines of both low and intermediate LET radiation. Compared to TK6, WTK1 has an enhanced X-ray survival, and is also more resistant to cell killing by {alpha}-particles. The hprt locus is more mutable in WTK1 than in TK6 by both X-rays and {alpha}-particles. WTK1 is also more mutable by {alpha}-particles than by X-rays at the hprt locus. X-ray-induced mutation at the heterozygous tk locus in WTK1 is about 25 fold higher than in TK6, while {alpha}-particle-induced mutation is nearly 50 fold higher at this locus. Also, the slowly growing tk- mutants, which comprise the majority of spontaneous and X-ray-induced tk- mutants of TK6, were not induced significantly by {alpha}-particles. Previously, we showed that TK6 has a reduced capacity for recombination compared with WTK1, and therefore, these ...

Science.gov (United States)

Serum growth hormone (GH) was suppressed in female rats bearing mammary tumors induced by 7, 12, dimethylbenz(a)anthracene (DMBA) or N-nitrosomethylurea(NMU). Serum GH was suppressed due to treatment with a human GH analog produced by the plerocercoid stage of the tapeworm Spirometra mansonoides. Rats treated with plerocercoid growth factor (PGF) via plerocercoid infection had accelerated growth rates despite marked reductions in GH levels. Approximately two-thirds of the mammary tumors induced by either DMBA or NMU regressed during three weeks of exposure to PGF while most of the control tumors continued to grow. The data support an important regulatory role for GH in growth of mammary tumors in rats. PMID:3019224

UK PubMed Central (United Kingdom)

In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion...Full Text Available

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In order to understand the role of EGF in the development of human mammary epithelial tissue, we analysed the binding of /sup 125/I-EGF to sections of breast cancer biopsies. A mean specific /sup 125/I-EGF binding of 8.9 fmol per mg protein was estimated in thin sections of 17 breast cancer biopsies. Microautoradiographic analysis of /sup 125/I-EGF binding to the tissue sections was applied to demonstrate that EGF was bound predominantly to mammary epithelial cells. The binding was clearly correlated to the number of mitoses of mammary epithelial cells in the same samples. The highest EGF binding and proliferation rates were found in biopsies from breast cancer with axillary lymph-node metastases.

British Library Electronic Table of Contents (United Kingdom)

Mammary glands are special tissue characterized by proliferation of the epithelium, during puberty and pregnancy and by programmed cell death, during involution. In this study, apoptosis was identified by TUNEL staining and then related to cell proliferation, as determined by Ki-67 staining. The apoptotic index was at its highest at 8 days of involution, whereas the proliferation index was at its highest during lactation. Caspase-3 was immunolocalised only in mast cells and along the basal membrane in the mammary tissue at -10 days from lambing, 150 days of lactation and at 8 days of involution. This finding could indicate that caspase-3 is not involved in sheep mammary gland apoptosis, but that other proteins - such as apoptosis inducing factor (AIF) - can trigger apoptosis, through the m...

UK PubMed Central (United Kingdom)

We report for the first time a case of a 54 years old man with a fatal motorcycle accident due to an external bleeding compression of left internal mammary artery graft to the left anterior descending...Full Text Available

Science.gov (United States)

Current models of DNA repair of biological damage are reviewed correlating the similarity between carcinogenesis and mutagenesis theories. (PCS)

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Pd/sub 2/Si layers produced by evaporation or sputtering onto silicon substrates were examined by high resolution electron microscopy, microdiffraction, X-ray, energy loss and Auger spectroscopy. The Si-Pd/sub 2/Si interfaces produced by evaporation were in all cases rougher and more polycrystalline than those produced by sputtering. X-ray microanalysis showed the predictable variation in palladium distribution across the interface but quantification did not produce the expected palladium-to-silicon ratios, primarily because of probe broadening and X-ray-induced fluorescence. Energy loss spectra showed plasmon energy shifts and changes in Si L edge shape due to bond formation with palladium. Auger data provided evidence for a small amount of oxygen at the Si-Pd/sub 2/Si interface. Electrical measurements of the ideality factor for Schottky barriers made from the materials produced higher values for the rougher evaporation-formed interfaces consistent with ...

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Current information suggests that chemical carcinogenesis is a multistep process with one of the best studied models in this regard being the two-stage carcinogenesis system using mouse skin. The effects of several carcinogens and tumor promoters in various sequences of application were studied to examine the nature of the process. The actions of several tumor inhibitors were compared. (ACR)

Science.gov (United States)

Apoptosis and Proliferation During DicWoroacetic Acid (DCA) Induced Hepatocellular Carcinogenesis in the F344 Male Rat Chlorine, introduced into public drinking \\\\'ater supplies for disinfection, can react with organic compounds in surface waters to form toxic by-prod...

UK PubMed Central (United Kingdom)

In addition to the well documented role of cytokines in mediating tissue-level interactions, it is now clear that matrix macromolecules fulfil a complementary regulatory function. Data highlighted in...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe lactogenic hormones prolactin (PRL) and placental lactogens (PL) play central roles in reproduction and mammary development. Their actions are mediated via binding...Full Text Available

British Library Electronic Table of Contents (United Kingdom)

The chemopreventive efficacy of turmeric has been established in experimental systems. However, its mechanism(s) of action are not fully elucidated in vivo. The present study investigates the mechanism of turmeric-mediated chemoprevention in 7,12-dimethylbenz(a)anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis at 2, 4, 6, 10 and 12?weeks. Dietary turmeric (1%) led to decrease in DMBA-induced tumor burden and multiplicity, and enhanced the latency period in parallel, to its modulatory effects on oncogene products and various cellular responses during HBP tumorigenesis. DMBA-induced expression of ras oncogene product, p21 and downstream target, the mitogen-activated protein kinases were significantly decreased by turmeric during HBP carcinogenesis. Turmeric also diminished ...

UK PubMed Central (United Kingdom)

Aims: To study the expression of nuclear β catenin in patients with colorectal cancer, colorectal adenoma, and colorectal polyps to elucidate its role in carcinogenesis, and its...Full Text Available

UK PubMed Central (United Kingdom)

BackgroundThe zebrafish is recognized as a versatile cancer and drug screening model. However, it is not known whether the estrogen-responsive genes and signaling pathways that are...Full Text Available

UK PubMed Central (United Kingdom)

Chronic colonization of the human stomach by Helicobacter pylori, a Gram-negative bacterium, is the major cause of chronic gastritis, peptic ulcers and gastric cancer. Recent...Full Text Available

UK PubMed Central (United Kingdom)

AIM: To investigate the relation of Fas and Fas ligand (FasL) protein expression with carcinogenesis and metastasis of gastric carcinoma.METHODS: Immunohistochemistry was used to detect Fas and...Full Text Available

International Nuclear Information System (INIS)

The three projects of the research program are aimed at the epidemiological study of long-term radiation effects in patients injected with radium-224. They are: late effects in "2"2"4Ra treated ankylosing spondylitis patients, late effects in "2"2"4Ra treated juvenile and adult patients, and epidemiology of radiation carcinogenesis. The data from these patients are a unique source of information for risk analysis of incorporated bone seeking radionuclides in man. (R.P.) 5 refs., 3 tabs.

Science.gov (United States)

Elution profiles of total lipoproteins, apolipoprotein B (apoB) concentrations in lipoproteins, and plasma triglyceride (TG) levels were examined in early-, late-, and non-lactating cows. Additionally, arteriovenous (A-V) differences were also measured to elucidate the uptake of TG and apoB-containing lipoproteins in mammary gland. Non-lactating cows showed three major peaks corresponding to triglyceride-rich lipoprotein (TRL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fraction, whereas both early- and late-lactating cows revealed two peaks corresponding to TRL and HDL. The peak area of TRL in early- and late-lactating cows were significantly (p < 0.05) smaller than that in non-lactating cows. The plasma TG levels and apoB-48 concentrations of TRL in early- and late-lactating cows were also significantly (p < 0.01) lower. Furthermore, early lactating cows showed significantly (p < 0.05) larger A-V differences in both plasma TG and ...

British Library Electronic Table of Contents (United Kingdom)

Estrogen metabolism is suggested to play an important role in estrogen-induced breast carcinogenesis. Epidemiologic studies suggest that diets rich in phytoestrogens are associated with a reduced risk of breast cancer. Phytoestrogens are biologically active plant compounds that structurally mimic 17b-estradiol (E2). We hypothesize that phytoestrogens, may provide protection against breast carcinogenesis by altering the expression of estrogen-metabolizing enzymes cytochrome P450 1A1 (Cyp1A1) and 1B1 (Cyp1B1). Cyp1A1 and Cyp1B1 are responsible for the metabolism of E2 to generate 2-hydroxyestradiol (2-OHE2) and 4-hydroxyestradiol (4-OHE2), respectively. Studies suggest that 2-OHE2 and 2-methoxyestradiol may protect against breast carcinogenesis, while 4-OHE2 is carcinogenic in rodent models....

UK PubMed Central (United Kingdom)

A total of 213 treated and 16 control monkeys comprising 12 experimental groups was evaluated for determination of the long-term (10 years) effects of various dosages of a variety of synthetic oral...Full Text Available

UK PubMed Central (United Kingdom)

Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover,...Full Text Available

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The book is divided into two approximately equal parts. The first four chapters are relatively lengthy and cover the basic principles of radiation biology, carcinogenesis and therapy, along with a brief introduction to radiological physics to orient the reader without background in this specialized related discipline. The remainder consists of twenty-four relatively brief chapters, each covering the radiation biology of a specific organ, tissue, or systems tissues, with emphasis on the tumorigenic and tumoricidal action of ionizing radiations.

UK PubMed Central (United Kingdom)

BackgroundAs EBV-associated gastric cancer has unique features that are different from EBV (-) gastric cancer, EBV is considered to have a key role in gastric carcinogenesis. It...Full Text Available

UK PubMed Central (United Kingdom)

Experimental studies have shown that two main estrogen metabolites hydroxylated by CYP1A1 and CYP1B1 in the breast differentially affect breast cell proliferation and carcinogenesis. Although 16α-hydroxyestrone...Full Text Available

International Nuclear Information System (INIS)

Daily exposures of adult beagle dogs to inhaled radon daughters and to uranium ore dust for 4-1/2 to 6 yr have produced respiratory tract carcinomas, at similar cumulative working level months (WLM) of exposures to those which induced carcinomas in uranium miners. Biological data from the beagle-dog experiments can therefore be used for prediction of carcinogenic risk under changing exposure conditions in future uranium miners.

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Glycosaminoglycan synthesis by two subpopulations of a mouse mammary tumor cell line was compared. The two sublines express distinctly different growth characteristics in vitro and in vivo which indicate differences in growth regulation. Newly made glycosaminoglycans were recovered from the culture media, the cell surfaces, and residual cellular material. The cell population which grows more aggressively in vivo (+SA subline, a subline that grows in soft agarose) incorporated about 8 times more (/sup 14/C)glucosamine per cell into total glycosaminoglycans than did the slower-growing population (-SA subline, which does not grow in soft agarose). Appropriate control experiments indicated that the apparent difference in rates of synthesis was not due to discrepancies in glucosamine uptake. The main residual cellular molecule labeled was heparan sulfate, but the predominant molecule at the cell surface and in the culture fluid was hyaluronic acid. Overall, +SA cells ...

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The distribution of lead in lactating mice and suckling offspring was studied with whole body autoradiography at 4 and 24 h after a single intravenous injection of {sup 203}Pb (50 mmol Pb/kg) to the dams. In the lactating mice on day 14 of lactation, the highest uptake of radioactivity at 4 h after administration was recorded in renal cortex, skeleton and liver. A high uptake was also evident in the mannary gland. At 24 h after administration, the radioactivity had decreased in most organs except in the skeleton. In the suckling pups, exposed to lead only via dams` milk for 24 h, the highest level of radioactivity was present in the intestinal mucosa and a much lower level of radioactivity was present in the skeleton. The mammary glands from mice given three daily intravenous injections of 240 {mu}mol Pb/kg were examined with X-ray microanalysis. At 4 h after the last injection, lead was found associated with casein micelles both inside the alveolar cell and in the ...

CERN Document Server

In longitudinal and spatial studies, observations often demonstrate strong correlations that are stationary in time or distance lags, and the times or locations of these data being sampled may not be homogeneous. We propose a nonparametric estimator of the correlation function in such data, using kernel methods. We develop a pointwise asymptotic normal distribution for the proposed estimator, when the number of subjects is fixed and the number of vectors or functions within each subject goes to infinity. Based on the asymptotic theory, we propose a weighted block bootstrapping method for making inferences about the correlation function, where the weights account for the inhomogeneity of the distribution of the times or locations. The method is applied to a data set from a colon carcinogenesis study, in which colonic crypts were sampled from a piece of colon segment from each of the 12 rats in the experiment and the expression level of p27, an important cell cycle ...

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The usefulness of the mouse, rat, and Syrian golden hamster as experimental models for studies of the development of respiratory tract cancer is considered. Three different application methods for examining the effects of environmental chemicals on the respiratory tract in these species are discussed: implantation, intratracheal instillation, and inhalation. The results of various investigations are presented to demonstrate that each particular method has both advantages and disadvantages. The techniques are also considered in comparison with the human situation and in the light of obtaining the most valid data for extrapolation to man. Brief attention is paid to the relevance to respiratory tract carcinogenesis of more recently developed organ and cell culture systems.

British Library Electronic Table of Contents (United Kingdom)

Abstract Septins are highly conserved cytoskeletal GTP-binding proteins implicated in numerous cellular processes from apoptosis to vesicle trafficking. Septins have been associated with leukemia and solid tumor malignancies, including breast, ovarian, and prostate. We previously reported that high SEPT9_i1 expression in human mammary epithelial cell lines (HMECs) led to malignant cellular phenotypes such as increased cell proliferation, invasiveness, motility, and genomic instability. Our goal here was to better understand how SEPT9_i1 expression might contribute to genomic instability and malignant progression. First, we confirmed that even transient expression of SEPT9_i1 was sufficient to increase aneuploidy in HMECs. We then analyzed SEPT9_i1 by immunoprecipitation and immunofluoresce...

British Library Electronic Table of Contents (United Kingdom)

Two ent-rosane- (cuzcol, 1 and 6-dehydroxycuzcol, 2) and a abietatriene- (salvadoriol, 3) type diterpenoids have been isolated from Maytenus cuzcoina and Crossopetalum uragoga, respectively, along with five known diterpene compounds (4-8). Their stereostructures have been elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR techniques, and computational data. The absolute configuration of cuzcol was determined by application of Riguera ester procedure. This is the first instance of isolation of ent-rosane diterpenoids from species of the Celastraceae. The isolated diterpenes were found to be potent anti-tumour-promoter agents, and carnosol (7) also showed a remarkable chemopreventive effect in an in vivo two-stage carcinogenesis model.

International Nuclear Information System (INIS)

Probable risks for the occurrence of somatic effects due to diagnostic radiology and nuclear medicine are summarised. The biological background of radiation carcinogenesis and epidemiological results are discussed. At the Leiden University Medical Centre the average effective dose per examination due to diagnostic radiology and nuclear medicine amount to 0.95 and 4.4 mSv, respectively. These values correspond well with the average values of 0.82 and 3.0 mSv reported for The Netherlands as a whole. Since radiological examinations are performed at a much larger frequency than nuclear medicine the relative collective dose for the first type of examinations is higher than the latter. Risk for occurency of malignancies are at least one order of magnitude lower than the hypothetical risk due to the background radiation typical of The Netherlands.

British Library Electronic Table of Contents (United Kingdom)

A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the...

International Nuclear Information System (INIS)

Simultaneous exposures of rats and hamsters to inhaled radon daughters, with and without uranium ore dust, were performed daily for five months. Pulmonary pathology developing in 6 to 13 mo after cessation of daily exposures included interstitial fibrosis, emphysema, epithelial hyperplasia, squamous metaplasia, and malignant neoplasia. Rats showed a greater variety and more severe response to these uranium mine inhalation exposures than did hamsters. Inhalation of radon daughters with uranium ore dust displayed the site of greatest damage, including squamous carcinoma, from the nasopharynx to the lungs. Sixty percent of the rats exposed to radon daughters with ore dust developed primary pulmonary carcinomas, providing an appropriate short-term experimental animal model for investigation of respiratory tract carcinogenesis in uranium miners.

International Nuclear Information System (INIS)

Full text: Introduction. Children, especially premature infants and neonates, are at a much higher risk to obtain an X ray induced disturbance of life - particularly cancer. On the one hand this is due to their longer life expectancy and on the other hand it is due to their higher cell proliferation rate. The paediatric radiology unit of the Inselspital Bern recently installed some of the most advanced X ray equipment nowadays available. It is based on the two latest digital technologies: double read computed radiography (CR) and direct digital radiography (DR). Only the implementation of these digital radiography systems permits the digital acquisition and additionally the analysis of acquired data. The systematic analysis of large amounts of biometric data and exposition data is the basis for further dose reduction and a systematic quality control (QC). Patients are increasingly critical concerning radiation exposure - ...

DEFF Research Database (Denmark)

Colorectal cancer is the third most common malignant tumor and the fourth-leading cause of cancer death worldwide. The crucial role of fatty acids for a number of important biological processes suggests a more in depth analysis of inter-individual differences in fatty acid metabolizing genes as contributing factor to colon carcinogenesis. We examined the association between genetic variability in 43 fatty acid metabolism-related genes and colorectal risk in 1225 CRC cases and 2032 controls participating in the European Prospective Investigation into Cancer and Nutrition study. 392 single nucleotide polymorphisms were selected using pairwise tagging with an r(2) cutoff of 0.8 and a minor allele frequency of >5%. Conditional logistic regression models were used to estimate odds ratios and corresponding 95% confidence intervals. Haplotype analysis was performed using a generalized linear model framework. On the genotype level, HPGD, PLA2G6, and TRPV3 were ...

Science.gov (United States)

The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and retinoic acid receptor beta(2), by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza; 0.25 mg/kg body weight), all-trans retinoic acid (RA; given at 100 microg/kg body weight and 1 mg/kg body weight), and the combination of 5-Aza and the low-dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were done for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. Although all drug treatments limited the increase in the percentage of proliferating cell nuclear antigen-positive ...

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We developed a new breast surface coil for the supine position. The subjects consisted of 9 patients with breast cancer varying from 46 to 60 years of age (average: 52). The cancer image of the SPGR (CE+) method was compared with that of the FSMTC (MTC-SPGR (CE+)) method and that of the FSMTC (MTC-SPGR with fat-saturation (CE+)) method in the sagittal section after injection of Gd-DTPA (0.1 mmol/kg). Quantitative analyses were performed before and after injection of Gd-DTPA in 6 patients. Three patients were excluded from the quantitative analyses owing to the clear detection of tumors in the fat tissue. Signal intensity measurements were systematically performed in each region of interest (ROI), i.e. the cancer lesion, the surrounding mammary gland. Statistical analyses showed significant differences between the lesions using the FSMTC (MTC-SPGR (CE+)), and the FSMTC (MTC-SPGR with fat-saturation (CE+)) methods and the lesions using the SPGR (CE+) method after ...

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The effects of atrial natriuretic peptide (ANP), oxytocin (OT) and vasopressin (AVP) on guanylate cyclase activity and cyclic GMP accumulation were examined, since these hormones appear to be intimately associated with blood pressure and intravascular volume homeostasis. ANP was found to increase cyclic GMP accumulation in ten cell culture systems, which were derived from blood vessels, adrenal cortex, kidney, lung, testes and mammary gland. ANP receptors were characterized in intact cultured cells using {sup 125}I-ANP{sub 8-33}. Specific {sup 125}I-ANP binding was saturable and of high affinity. Scratchard analysis of the binding data for all cell types exhibited a straight line, indicating that these cells possessed a single class of binding sites. Despite the presence of linear Scatchard plots, these studies demonstrated that cultured cells possess two functionally and physically distinct ANP-binding sites. Most of the ANP-binding sites in cultured cells have a ...

International Nuclear Information System (INIS)

The "1"3"1-radioiodine use in Guanabara area, during 1972-1973, is analysed. References are made to the radiation levels delivered to thyroid, bone marrow and gonads in a population of 27000 people examined by tracer techniques, 190 submitted to hyperthyroidism treatment and 50 treated for thyroid cancer. The pertinent literature gives some data concerning radiation induced cancer (leukaemia and thyroid cancer). By this, it was possible to estimate the probability of tumour occurrence in that population, assuming a linear relationship between dose and effect. The conclusions are the followings: 1 - there are many duties in this field at the present; 2 - the leukaemia incidence related to the 131-radioiodine use is negligible, either in diagnostic or therapeutic modalities; 3 - the possibility of thyroid tumors induced by radiation is real, specially in hyperthyroidism treatment; 4 - the use of tracer techniques that cause lower irradiation to the pacient is advisable, because it isn't ...

International Nuclear Information System (INIS)

Understanding risks from exposures to carcinogens and other chemicals depends upon measurement of their dose to target tissues and their reactivity with critical macromolecules. The authors have used AMS detection of radio-isotopes to assess doses and reactivities at low, environmentally relevant doses. Several biomedical investigations show the effectiveness of quantification of biologically important events at extremely high sensitivity with AMS. Specifically, they have measured the addition of environmental carcinogens such as 2-amino-3,8-dimethylimidazo[4,5-f]-quinoaxaline (MelQx), a chemical found in cooked food, to DNA at concentrations relevant to human exposure. Other low level detection problems in biology, such as immunoassay assessment of small environmental chemicals, is being developed with attomole sensitivity. AMS also aids the assessment of genotoxic risks from chemicals by quantifying the binding of labeled chemicals to DNA. The very toxic and potent carcinogen, ...

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Many assays for oncogenic transformation have been developed ranging from those in established rodent cell lines where morphological alteration is scored, to those in human cells growing in nude mice where tumor invasiveness is scored. In general, systems that are most quantitaive are also the least relevant in terms of human carcinogenesis and human risk estimation. The development of cell culture systems has made it possible to assess at the cellular level the oncogenic potential of a variety of chemical, physical and viral agents. Cell culture systems afford the opportunity to identify factors and conditions that may prevent or enhance cellular transformation by radiation and chemicals. Permissive and protective factors in radiation-induced transformation include thyroid hormone and the tumor promoter TPA that increase the transformation incidence for a given dose of radiation, and retinoids, selenium, vitamin E, and 5-aminobenzamide that inhibit the expression ...

Energy Technology Data Exchange (ETDEWEB)

The use of hypothesis which assumes a dose / harmful effect relationship without a limit allows the calculation of risks attributable to doses too small to produce detectable, harmful biological effects. The daughter product of this hypothesis is ALARA concept which requires that the dose received is kept as low as reasonably achievable. This concept of prudent avoidance is generally accepted by international radiation protection organisations and universally applied by radiation health professionals. The acceptance of a hypothesis which assumes that a single nuclear event can cause carcinogenesis, has generated levels of anxiety which may have resulted in significant detriment to those possibly exposed to ionising radiation. The anxiety generated may have caused more detriment and a higher death rate than the worst case ` theoretical` value calculated using the Linear or Quadratic Linear Hypothesis. Information selected from reports and comments in relevant ...

International Nuclear Information System (INIS)

For the purpose of risk estimates from radiation carcinogenesis including leukemogenesis and radiation genetic effects, the biological significant dose is not the tissue kerma in air but the absorbed dose in organ or tissue with respect to carcinogenic and leukemogenic effects or genetic effects. In order to estimate organ or tissue dose from the tissue kerma in air, a ratio of the organ or tissue dose to the tissue kerma in air for survivors in Hiroshima and Nagasaki was calculated with the aid of the Snyder's mathematical phantoms constructed so as to simulate the body shape of survivors aged 5, 10 years old and adult at the time of atomic bomb detonations. The ratios were corrected for the angular distribution of atomic bomb radiations, assuming an anisotropic angular distribution for the survivors exposed to the atomic bombs in open air and the isotropic distribution for the survivors incide a Japanese house or other structures. The resultant ratios are ...

International Nuclear Information System (INIS)

Metabolic profile is an important biological marker of neoplastic processes not only in the tumor itself but also in the host organism. The neuro-hormone melatonin has been implicated in the experiments as an oncostatic agent. Female Wistar:Han SPF rats (Velaz, Prague, Czech Republic) were irradiated continuously for 15 days using a daily gamma rays dose of 96 mGy. At the end of exposure one group of rats was administered 5 mg/kg b.w. of dimethylbenz/a/anthracene (DMBA) intragastrically. During the period of exposure to ionizing radiation a part of the animals was supplied with melatonin (M) at a concentration of 20 #mu#l/ml in drinking water. Selected parameters of lipid and carbohydrate metabolism and levels of selected hormones were determined 2, 30 and 100 days post-irradiation. The irradiation itself caused only small changes in tissue lipids. The application of a single low dose (subthreshold from the point of view of induction of mammary tumors) of DMBA ...

Energy Technology Data Exchange (ETDEWEB)

Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many species of mice and rats but not in humans ...

International Nuclear Information System (INIS)

Exposure of cells to light of less than 320 nanometers wavelengths may lead to lethal lesions and perhaps carcinogenesis. Many organisms have evolved mechanisms to repair U.V. light-induced damage. Organisms such as deep-sea bacteria are presumably never exposed to U.V. light and perhaps occasionally to visible from bioluminescence. Thus, the repair of U.V. damage in deep-sea bacterial DNA might be inefficient and repair by photoreactivation unlikely. The bacteria utilized in this investigation are temperature sensitive and barophilic. Four deep-sea isolates were chosen for this study: PE-36 from 3584 m, CNPT-3 from 5782 m, HS-34 from 5682 m, and MT-41 from 10,476 m, all are from the North Pacific ocean. The deep-sea extends from 1100 m to depths greater than 7000 m. It is a region of relatively uniform conditions. The temperature ranges from 5 to -1"0C. There is no solar light in the deep-sea. Deep-sea bacteria are sensitive to U.V. light; in fact more sensitive ...

International Nuclear Information System (INIS)

The development of leukemia and thyroid cancer is characterized by activation of the abl oncogene and ret oncogene, respectively. In order to clarify the relationship between these gene aberrations and radiation, the pro-myelogenous leukemia-derived cell line HL60 and the thyroid cancer-derived cell line 8505C, were irradiated in vitro with 100Gy of X-rays. RNA was then extracted from 10"8 cells of the respective cell lines and examined by the reverse transcription PCR method for rearrangements of abl and ret genes. Five kinds of positive bands were observed in the HL-60 cells irradiated with 100Gy of X-ray. Similarly, six positive bands were also observed in the 8505C cells irradiated with 100Gy. In vitro X-irradiation activation of oncogenes found in radiation induced cancers imply that gene rearrangement by X-rays is involved in the development of malignant tumors. Furthermore, in an experiment to detect radiation effects in A-bomb survivors, RNA was extracted from about 10"7 ...

International Nuclear Information System (INIS)

In the medical and occupational exposures, there is a tradition to use the genetically significant dose as an index of harm to the population although it only includes the genetical effects from ionizing radiations. A similar significant dose for somatic effects such as radiation leukemogenesis and carcinogenesis should be added to the genetically significant dose in order to approach an index of total harm to the population from medical and occupational exposures. For this purpose, leukemia and malignant significant factors were determined based on the induction of malignant diseases including leukemia for the atomic bombs in Hiroshima and Nagasaki and the life expectancy of individuals subject to medical examinations or treatments as well as radiation workers, taking account of the possibility of their deaths due to other diseases or accidents during a latent period of malignant diseases. The resultant significant factors were tabulated as a function of life ...

Energy Technology Data Exchange (ETDEWEB)

Background: Cu-diacetyl-bis(N{sup 4}-methylthiosemicarbazone) [Cu-ATSM], although excellent for oncology applications, may not be suitable for delineating cardiovascular or neurological hypoxia. For this reason, new Cu hypoxia positron emission tomography (PET) imaging agents are being examined to search for a higher selectivity for hypoxic or ischemic tissue at higher oxygen concentrations found in these tissues. Two approaches are to increase alkylation or to replace the sulfur atoms with selenium, resulting in the formation of selenosemicarbazones. Methods: Three {sup 64}Cu-labeled selenosemicarbazone complexes were synthesized and one was screened for hypoxia selectivity in vitro using EMT-6 mouse mammary carcinoma cells. Rodent biodistribution and small animal PET images were obtained from BALB/c mice implanted with EMT-6 tumors. One alkylated thiosemicarbazone was synthesized and examined. Results: Of the three bis(selenosemicarbazone) ligands synthesized and ...