Sample records for cocarcinogenesis
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International Nuclear Information System (INIS)
Fry, R.J.M.
1975-01-01
The long-term aims are concerned with various aspects of the natural history and biology of cancer, the mechanism of induction and of the advancement of time of appearance of tumors, the development of systems suitable for the assay of oncogenesis and cocarcinogenesis, and the elucidation of some of the factors important to the problem of extrapolation of estimates of risk made in experimental systems to the estimate of risk in man. It is necessary to have a number of test systems in order to study the various factors related to cocarcinogenesis; some of these are clearly tissue specific. The liver tumor system is clearly useful for certain compounds, and the liver is an excellent tissue for the study of the mechanisms of cocarcinogenesis. This year we report on the relatively rapid induction of what appears histologically to be carcinoma of the thyroid by aminotriazole. In a collaborative study with the Neutron and Gamma-Ray Toxicity Group, we have established a new example of synergism in carcinogenesis, namely between radiation and pituitary hormone(s) in the production of Harderian gland tumors. Not only does a synergistic effect on incidence occur, but also on the degree of malignancy of the tumor induced. We thus have three different model systems for the study of various aspects of cocarcinogenesis: various chemicals, including nononcogenic polycyclic hydrocarbons, in liver tumorigenesis; ionizing radiation and aminotriazole in thyroid tumorigenesis; and in conjunction with the JANUS Program, the interaction of radiation and hormones in the production of Harderian gland, mammary gland, and other tumors
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Arsenic is a recognized human skin, lung, and urinary bladder carcinogen, and may act as a cocarcinogen in the urinary bladder (with cigarette smoking) and skin (with UV light exposure). Possible modes of action of arsenic carcinogenesis/cocarcinogenesis include induction of DNA ...
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Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G.; Liu, Ke Jian
2013-01-01
Arsenic enhances genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic co-carcinogenesis, and DNA repair proteins such as poly (ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlyi...
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Ozone carcinogenesis in vitro and its co-carcinogenesis with radiation
International Nuclear Information System (INIS)
Borek, C.
1988-01-01
Ozone (O/sub 3/), a reactive species of oxygen, is an important natural constituent of the atmosphere. Background levels of ozone in the lower atmosphere may range up to 0.1 ppm and are modified by geographic elevation, solar radiation and climatic conditions. Since some ozone effects are radiomimetic, its actions may be enhanced in the presence of ionizing radiation from background and/or manmade sources. While stratospheric ozone spares the earth from excess solar ultraviolet (UV) radiation, high levels of ozone in the environment are toxic and present a health hazard to man. Excess environmental exposure to ozone can result from a variety of sources. Ozone is a key component in oxidant smog and in the vicinity of high electric voltage equipment when in operation. Ozone is widely used as a disinfectant for air and water, in bleaches, waxes, textiles, oils. and inorganic synthesis. Enhanced levels of ozone are found in planes flying at high altitudes. Because of the toxic nature of ozone and its potential hazard to man, its levels in the environment are subject to government regulation. The current standard is set at an hourly average of 235 μg/m/sup 3/ (0.12 ppm) not to be exceeded more than once per year. Urban areas with high levels of photochemical smog (e.g. Southern California) may experience high ambient ozone levels which can reach 0.5 ppm
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Division of Biological and Medical Research annual research summary, 1983
International Nuclear Information System (INIS)
Barr, S.H.
1984-08-01
This research summary contains brief descriptions of research in the following areas: (1) mechanisms of hepatocarcinogenesis; (2) role of metals in cocarcinogenesis and the use of liposomes for metal mobilization; (3) control of mutagenesis and cell differentiation in cultured cells by tumor promoters; (4) radiation effects in mammalian cells; (5) radiation carcinogenesis and radioprotectors; (6) life shortening, tumor induction, and tissue dose for fission-neutron and gamma-ray irradiations; (7) mammalian genetics and biostatistics; (8) radiation toxicity studies; (9) hematopoiesis in chronic toxicity; (10) molecular biology studies; (11) chemical toxicology; (12) carcinogen identification and metabolism; (13) metal metabolism and toxicity; and (14) neurobehavioral chronobiology
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Division of Biological and Medical Research annual research summary, 1983
Energy Technology Data Exchange (ETDEWEB)
Barr, S.H. (ed.)
1984-08-01
This research summary contains brief descriptions of research in the following areas: (1) mechanisms of hepatocarcinogenesis; (2) role of metals in cocarcinogenesis and the use of liposomes for metal mobilization; (3) control of mutagenesis and cell differentiation in cultured cells by tumor promoters; (4) radiation effects in mammalian cells; (5) radiation carcinogenesis and radioprotectors; (6) life shortening, tumor induction, and tissue dose for fission-neutron and gamma-ray irradiations; (7) mammalian genetics and biostatistics; (8) radiation toxicity studies; (9) hematopoiesis in chronic toxicity; (10) molecular biology studies; (11) chemical toxicology; (12) carcinogen identification and metabolism; (13) metal metabolism and toxicity; and (14) neurobehavioral chronobiology. (ACR)
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Co-carcinogenesis: Human Papillomaviruses, Coal Tar Derivatives, and Squamous Cell Cervical Cancer
Directory of Open Access Journals (Sweden)
Harry W. Haverkos
2017-11-01
Full Text Available Cervical cancer (CC is the fourth most common cancers among women worldwide. Human papillomaviruses (HPVs play a major role in the etiology of CC, with several lines of epidemiologic and experimental evidence supporting a role for non-viral (co-carcinogens and host genetic factors in controlling the risk for progression to neoplasia among HPV-infected individuals. The role of co-carcinogens in the development of CC is significant in the developing world where poor sanitation and other socio-economic conditions increase the infectious cancer burden. Here, we discuss how exposure to environmental factors such as coal tar derivatives from cigarette smoking, tar-based sanitary products, and inhaled smoke from biomass-burning stoves, could activate host pathways involved in development of HPV-associated squamous cell cancers in resource-limited settings. Understanding interactions between these pathways with certain oncogenic HPV genotypes may guide implementation of strategies for control and treatment of HPV-associated cancers that develop in populations at high risk of exposure to various co-carcinogens.
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Role of metals in cocarcinogenesis and the use of liposomes for metal mobilization
International Nuclear Information System (INIS)
Rahman, Y.E.; Jonah, M.M.; Lagocki, P.A.; Cerny, E.A.
1985-01-01
The role of arsenic in skin tumorigenesis has been addressed. Arsenic does not function as a second-stage promoter; instead it appears to serve as a cocarcinogen. A population of preneoplastic focus cells derived from dielhylnitrosamine treated rats were isolated and some properties characteristic of this group of cells were identified. A new lipophilic chelator, N,N'-bis[2-hydroxybenzyl]-ethylenediamine- N,N'-diacetic acid, has been found to be far superior to DF, the iron chelator of choice in clinical use since 1960. 3 refs. (DT)
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Radiation carcinogenesis. Progress report IV, 15 March 1976--15 May 1977
International Nuclear Information System (INIS)
Warren, S.; Gates, O.
1977-01-01
The series of parabiont and irradiated rats has been completed, the lesions diagnosed and the data pertinent to tumors computerized and partly analyzed. The same series yielded 74 percent incidence of cataract in the irradiated partner following a whole-body dose of 1000 R with 0.2 percent in the shielded partner and also in controls. There was no abscopal effect. Other structures of the eye beside the lens, particularly the retina, showed extensive radiation damage. Parabiosis increased the incidence rate of leukemia from one percent in control single rats to five percent. Irradiation of one partner decreased the rate to 2.5 percent. Similar effects were noted for solid lymphoid tumors. A pilot study of prostatic cancer in irradiated parabiont rats demonstrated a tenfold increase in incidence. Experimental protocols bearing on cocarcinogenesis have been initiated in mice and rats, using radiation, asbestos and chemical carcinogens, but no results have been as yet obtained. We have obtained additional evidence suggesting the importance of prolactin as a cocarcinogen with radiation for induction of mammary tumors in the rat and are continuing our collaborative study of hormonal aasays in the blood of parabiont rats
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1980-09-01
cats exposed to methylnitrosourea, Cancer Res., 38, 996, 1978. 12. Prehn, R.T’, Function of depressed immunologic reactivity during carcinogenesis, 3...4/8 UDH 50.0 N.D. 5.1 4/8 MAMA 3.6 N.D. 900.0 2/16 B(a)P 10.0 39 1.0 6/10 MMS 0.1 2500 0 0/6 U.V. 40 J.m-2 78 20.0 4/6 137Cs 100 r 39 13.1 3/7...intracellular distribution and binding of benzo(a)pyrene in human dysloid fibroblasts. Cancer Letters 10:57-65. 2. G. Milo, G.A. Ackerman, and I
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Division of Biological and Medical Research annual report 1978
Energy Technology Data Exchange (ETDEWEB)
Rosenthal, M.W. (ed.)
1978-01-01
The research during 1978 in the Division of Biological and Medical Research, Argonne National Laboratory, is summarized. Studies related to nuclear energy include responses of beagles to continuous low-level /sup 60/Co gamma radiation, and development of leukemic indicators; comparison of lifetime effects in mice of low-level neutron and /sup 60/Co gamma radiation; genetic effects of high LET radiations; and metabolic and therapeutic studies of heavy metals. Studies of nonnuclear energy sources deal with characterization and toxicological evaluation of effluents of fluidized bed combustion and coal gasification; electrical storage systems; electric fields associated with energy transmission; and development of population projection models and assessment of human risk. Basic research studies include fundamental structural and biophysical investigations; circadian rhythms; mutagenesis in bacteria and mammalian cells; cell killing, damage, and repair in mammalian cells; carcinogenesis and cocarcinogenesis; the use of liposomes as biological carriers; and studies of environmental influences on life-span, physiological performance, and circadian cycles. In the area of medical development, proteins in urine and tissues of normal and diseased humans are analyzed, and advanced analytical procedures for use of stable isotopes in clinical research and diagnosis are developed and applied. The final sections of the report cover support facilities, educational activities, the seminar program, staff talks, and staff publications.
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Division of Biological and Medical Research annual report 1978
International Nuclear Information System (INIS)
Rosenthal, M.W.
1978-01-01
The research during 1978 in the Division of Biological and Medical Research, Argonne National Laboratory, is summarized. Studies related to nuclear energy include responses of beagles to continuous low-level 60 Co gamma radiation, and development of leukemic indicators; comparison of lifetime effects in mice of low-level neutron and 60 Co gamma radiation; genetic effects of high LET radiations; and metabolic and therapeutic studies of heavy metals. Studies of nonnuclear energy sources deal with characterization and toxicological evaluation of effluents of fluidized bed combustion and coal gasification; electrical storage systems; electric fields associated with energy transmission; and development of population projection models and assessment of human risk. Basic research studies include fundamental structural and biophysical investigations; circadian rhythms; mutagenesis in bacteria and mammalian cells; cell killing, damage, and repair in mammalian cells; carcinogenesis and cocarcinogenesis; the use of liposomes as biological carriers; and studies of environmental influences on life-span, physiological performance, and circadian cycles. In the area of medical development, proteins in urine and tissues of normal and diseased humans are analyzed, and advanced analytical procedures for use of stable isotopes in clinical research and diagnosis are developed and applied. The final sections of the report cover support facilities, educational activities, the seminar program, staff talks, and staff publications
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Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G; Jian Liu, Ke
2013-08-01
Arsenic enhances the genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic cocarcinogenesis, and DNA repair proteins such as poly(ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlying arsenic inhibition of DNA repair. We report herein that arsenite-generated ROS/RNS inhibits PARP-1 activity in cells. Cellular exposure to arsenite, as well as hydrogen peroxide and NONOate (nitric oxide donor), decreased PARP-1 zinc content, enzymatic activity, and PARP-1 DNA binding. Furthermore, the effects of arsenite on PARP-1 activity, DNA binding, and zinc content were partially reversed by the antioxidant ascorbic acid, catalase, and the NOS inhibitor, aminoguanidine. Most importantly, arsenite incubation with purified PARP-1 protein in vitro did not alter PARP-1 activity or DNA-binding ability, whereas hydrogen peroxide or NONOate retained PARP-1 inhibitory activity. These results strongly suggest that cellular generation of ROS/RNS plays an important role in arsenite inhibition of PARP-1 activity, leading to the loss of PARP-1 DNA-binding ability and enzymatic activity. Copyright © 2013 Elsevier Inc. All rights reserved.
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International Nuclear Information System (INIS)
Chen, Jin-Yan; Chen, Wan-Nan; Jiao, Bo-Yan; Lin, Wan-Song; Wu, Yun-Li; Liu, Ling-Ling; Lin, Xu
2014-01-01
The risk of hepatocellular carcinoma (HCC) increases in chronic hepatitis B surface antigen (HBsAg) carriers who often have concomitant increase in the levels of benzo[alpha]pyrene-7,8-diol-9,10-epoxide(±) (BPDE)-DNA adduct in liver tissues, suggesting a possible co-carcinogenesis of Hepatitis B virus (HBV) and benzo[alpha]pyrene in HCC; however the exact mechanisms involved are unclear. The interaction between hepatitis B spliced protein (HBSP) and microsomal epoxide hydrolase (mEH) was confirmed using GST pull-down, co-immunoprecipitation and mammalian two-hybrid assay; the effects of HBSP on mEH-mediated B[alpha]P metabolism was examined by high performance liquid chromatography (HPLC); and the influences of HBSP on B[alpha]P carcinogenicity were evaluated by bromodeoxyuridine cell proliferation, anchorage-independent growth and tumor xenograft. HBSP could interact with mEH in vitro and in vivo, and this interaction was mediated by the N terminal 47 amino acid residues of HBSP. HBSP could greatly enhance the hydrolysis activity of mEH in cell-free mouse liver microsomes, thus accelerating the metabolism of benzo[alpha]pyrene to produce more ultimate carcinnogen, BPDE, and this effect of HBSP requires the intact HBSP molecule. Expression of HBSP significantly increased the formation of BPDE-DNA adduct in benzo[alpha]pyrene-treated Huh-7 hepatoma cells, and this enhancement was blocked by knockdown of mEH. HBSP could enhance the cell proliferation, accelerate the G1/S transition, and promote cell transformation and tumorigenesis of B[alpha]P-treated Huh-7 hepatoma cells. Our results demonstrated that HBSP could promote carcinogenic effects of B[alpha]P by interacting with mEH and enhancing its hydrolysis activity
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Differential sensitivities of cellular XPA and PARP-1 to arsenite inhibition and zinc rescue.
Ding, Xiaofeng; Zhou, Xixi; Cooper, Karen L; Huestis, Juliana; Hudson, Laurie G; Liu, Ke Jian
2017-09-15
Arsenite directly binds to the zinc finger domains of the DNA repair protein poly (ADP ribose) polymerase (PARP)-1, and inhibits PARP-1 activity in the base excision repair (BER) pathway. PARP inhibition by arsenite enhances ultraviolet radiation (UVR)-induced DNA damage in keratinocytes, and the increase in DNA damage is reduced by zinc supplementation. However, little is known about the effects of arsenite and zinc on the zinc finger nucleotide excision repair (NER) protein xeroderma pigmentosum group A (XPA). In this study, we investigated the difference in response to arsenite exposure between XPA and PARP-1, and the differential effectiveness of zinc supplementation in restoring protein DNA binding and DNA damage repair. Arsenite targeted both XPA and PARP-1 in human keratinocytes, resulting in zinc loss from each protein and a pronounced decrease in XPA and PARP-1 binding to chromatin as demonstrated by Chip-on-Western assays. Zinc effectively restored DNA binding of PARP-1 and XPA to chromatin when zinc concentrations were equal to those of arsenite. In contrast, zinc was more effective in rescuing arsenite-augmented direct UVR-induced DNA damage than oxidative DNA damage. Taken together, our findings indicate that arsenite interferes with PARP-1 and XPA binding to chromatin, and that zinc supplementation fully restores DNA binding activity to both proteins in the cellular context. Interestingly, rescue of arsenite-inhibited DNA damage repair by supplemental zinc was more sensitive for DNA damage repaired by the XPA-associated NER pathway than for the PARP-1-dependent BER pathway. This study expands our understanding of arsenite's role in DNA repair inhibition and co-carcinogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.
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Directory of Open Access Journals (Sweden)
Marione A. Moreira Souto
2006-06-01
of disease and necropsied. The main gross and microscopic alterations were found in identical areas of the UDT. They consisted of papillomas, transforming papillomas, and squamous cell carcinomas (SCCs. Metastases of SCCs to regional lymph nodes and other organs, such as liver and lungs, were also observed (18/30. Twenty-nine bovine had papillomas of various sizes in several areas of the UDT. The digestive papillomatosis ranged from mild (45%, to moderate (38%, to severe (17%. Three developing phases were observed microscopically in the examined papillomas: an early growing phase, a developing phase, and a regressing phase. In 16 cases, there was malignant transformation of papillomas into SCCs. The SCCs were solitary (12/30 or multiple (18/30 and were histologically well, moderately, or poorly differentiated. Grouping the distribution of SCCs of larger extension in the UDT into cranial region (base of the tongue, pharynx/oropharynx, and epiglottis, medial region (esophagus, and caudal region (cardia and rumen, the distribution was cranial in 39%, middle in 16%, and caudal in 45% of the cases. By the same grouping criteria, but considering the total number of times SCCs of varied extensions were diagnosed in the cranial, middle, and caudal regions, the percentages changed to 34%, 26%, and 40%, respectively. The epidemiological and histomorphological evidences found in this study are in agreement with the observations that point out the co-carcinogenesis between bovine papillomavirus type 4 infection and chemicals of bracken fern in the pathogenesis of the SCCs in the UDT of cattle. However, the presence of pre-neoplastic changes and SCCs in situ or in early stages of development, independently of the presence of papillomas, clearly indicates the possibility of development of SCCs from normal epithelium, probably due to the direct action of the chemical carcinogens contained in bracken fern.