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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Age-adjusted mortality rates were analyzed to examine the dose-response relation between ingested arsenic levels and risk of cancers and vascular diseases among residents in the endemic area of blackfoot disease, a unique peripheral vascular disease associated with long-term exposure to high-arsenic artesian well water and confined to the southwestern coast of Taiwan. The arsenic levels in well water determined in 1964-1966 were available in 42 villages of the study area, while mortality and population data during 1973-1986 were obtained from the local household registration offices and Taiwan Provincial Department of Health. Age-adjusted mortality rates from various cancers and vascular diseases by sex were calculated using the 1976 world population as the standard population. A significant dose-response relation was observed between arsenic levels in well water and cancers of the bladder, kidney, skin, and lung in both males and females, and cancers of the prostate and liver in males. However, there was no association for cancers of the nasopharynx, esophagus, stomach, colon, and uterine cervix, and for leukemia. Arsenic levels in well water were also associated with peripheral vascular diseases and cardiovascular diseases in a dose-response pattern, but not with cerebrovascular accidents. The dual effect of arsenic on carcinogenesis and arteriosclerosis and the interrelation between these two pathogenic mechanisms deserve more intensive study.
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PMID:Dose-response relation between arsenic concentration in well water and mortality from cancers and vascular diseases. 258 5

Arsenic is widely distributed throughout the animal and plant kingdoms and our environment where sources can be natural or anthropogenic. Agricultural uses of arsenic have declined recently, but it still has well-defined roles in industry. Small amounts of arsenic are metabolized in a variety of ways and are largely rapidly methylated and excreted by man and animals. Poisoning can occur and may follow an acute or chronic course. Toxic manifestations in man occur at the cellular level and may appear in many organ systems. Specific effects can often be demonstrated in the skin and in the vascular and nervous systems. Other toxic effects appear to include carcinogenesis, mutagenesis, and teratogenesis.
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PMID:Clinical and environmental aspects of arsenic toxicity. 352 97

Some metals are essential oligo-elements for man. However, if the body load of these same metal derivatives becomes excessive they may be responsible for deleterious effects, particularly cytotoxic ones. Metals are divided into four categories: potent carcinogens; presumptive carcinogens with a documented cocarcinogenic effect; ascertained cocarcinogens; metals with no demonstrated carcinogenic or cocarcinogenic effect. The most common tumors induced by metals are those of the lung. Arsenic induces cancer of the lung and skin, beryllium may induce lung cancer, the effects of cobalt are dubious, cadmium can induce cancer of the lung and, above all, prostate, the role of iron is uncertain, hexavalent chrome may induce cancer of the lung and nasal fossae, nickel is responsible for cancer of lung and nasal fossae. Our understanding of metal carcinogenesis is clearly insufficient and more experimental research and epidemiologic studies addressing this subject are needed.
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PMID:[Carcinogenic effect of metals]. 631 79

Sodium arsenite (As)-induced DNA damage was measured in human fetal lung fibroblasts (2BS cells) by an alkaline elution technique and a fluorometric DNA assay. Sodium arsenite at 1-5 microM produced DNA-protein crosslinks, while at 10 microM this effect was not observed. Deproteinization of DNA-protein complexes revealed protein-associated DNA-strand breaks. Both DNA-protein crosslinks and DNA-strand breaks were concentration-dependent; 3 microM As was the most efficient dose. Arsenic mediated DNA-protein interactions may play a major role in arsenic carcinogenesis, and the induced protein-associated DNA-strand breaks could provide an explanation for chromosome aberrations and sister-chromatid exchanges induced by arsenic in vivo and in vitro.
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PMID:Arsenic-induced DNA-strand breaks associated with DNA-protein crosslinks in human fetal lung fibroblasts. 768 11

Arsenic (As) is environmentally ubiquitous and an epidemiologically significant chemical related to certain human cancers. Dimethylarsinic acid (cacodylic acid; DMA) is one of the major methylated metabolites of ingested arsenicals in most mammals. To evaluate the effects of DMA on chemical carcinogenesis, we conducted a multiorgan bioassay in rats given various doses of DMA. One-hundred twenty-four male F344/DuCrj rats were divided randomly into 7 groups (20 rats each for groups 1-5; 12 rats each for groups 6 and 7). To initiate multiple organs and tissues, animals in groups 1-5 were treated sequentially with diethylnitrosamine (100 mg/kg body weight, i.p., single dose at the commencement) and N-methyl-N-nitrosourea (20 mg/kg body weight, i.p., 4 times, on days 5, 8, 11, and 14). Thereafter, rats received 1,2-dimethylhydrazine (40 mg/kg body weight, s.c., 4 times, on days 18, 22, 26, and 30). During the same period, the animals were sequentially administered N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05% in the drinking water, during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in the drinking water, during weeks 3 and 4; DMBDD treatment). After a 2-week interval, groups 2-5 were given 50, 100, 200, or 400 ppm DMA, respectively, in the drinking water. Groups 6 and 7, which were not given DMBDD treatment, received 100 and 400 ppm DMA during weeks 6-30. All rats were killed at the end of week 30. In the initiated groups (groups 1-5), DMA significantly enhanced the tumor induction in the urinary bladder, kidney, liver, and thyroid gland, with respective incidences in group 5 (400 ppm DMA) being 80, 65, 65, and 45%. Induction of preneoplastic lesions (glutathione S-transferase placental form-positive foci in the liver and atypical tubules in the kidney) was also significantly increased in DMA-treated groups. Ornithine decarboxylase activity in the kidneys of rats treated with 100 ppm DMA was significantly increased compared with control values (P < 0.001). In conclusion, DMA is acting as a promoter of urinary bladder, kidney, liver, and thyroid gland carcinogenesis in rats, and we speculate that this may be related to cancer induction by As in humans.
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PMID:Cancer induction by an organic arsenic compound, dimethylarsinic acid (cacodylic acid), in F344/DuCrj rats after pretreatment with five carcinogens. 788 21

Arsenic is a naturally occurring metalloid that has been associated with increased incidence of human cancer in certain highly exposed populations. Arsenic is released to the environment by natural means such as solubilization from geologic formations into water supplies. It is also released to occupational and community environments by such activities as nonferrous ore smelting and combustion of fuels containing arsenic. Several lines of evidence indicate that arsenic acts indirectly with other agents to ultimately enhance specific genotoxic effects that may lead to carcinogenesis. Work described here indicates that arsenite specifically potentiates chromosomal aberrations induced by a DNA crosslinking agent, 1,3-butadiene diepoxide, but does not effect the induction of sister chromatid exchanges under the same treatment conditions. It is proposed that the specific co-clastogenic effects of arsenite seen here may be mediated by its interference with DNA repair activities. Further understanding of the mechanism by which arsenic interacts with other environmental agents will result in more accurate estimates of risk from exposure to arsenic.
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PMID:Enhancement of chromosomal damage by arsenic: implications for mechanism. 814 51

Induction of cancer by inorganic arsenic occurs inconsistently between species and between routes of exposure, and it exhibits different dose-response relationships between different target organs. Inhaled or ingested arsenic causes cancer in humans but not in other species. Inhaled arsenic primarily induces lung cancer, whereas ingested arsenic induces cancer at multiple sites, including the skin and various other organs. Cancer potency appears to vary by route of exposure (ingestion or inhalation) and by organ site, and increases markedly at higher exposures in some instances. To understand what might explain these inconsistencies, we reviewed several hypotheses about the mechanism of cancer induction by arsenic. Arsenic disposition does not provide satisfactory explanations. Induction of cell proliferation by arsenic is a mechanism of carcinogenesis that is biologically plausible and compatible with differential effects for species or differential dose rates for organ sites. The presence of other carcinogens, or risk modifiers, at levels that correlate with arsenic in drinking water supplies, may be a factor in all three inconsistencies: interspecies specificity, organ sensitivity to route of administration, and organ sensitivity to dose rate.
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PMID:Carcinogenic risks of inorganic arsenic in perspective. 889 90

Arsenic, a human carcinogen, possesses a serious environmental threat but the mechanism of its toxicity remains unclear. Knowledge of how arsenic induces cell death and how cells escape the death path may help to understand arsenic carcinogenesis. We have investigated the nature of sodium arsenite-induced cell death in Chinese hamster ovary K1 cells. Following phosphate-citric acid buffer extraction, apoptotic cells with lower DNA content than the G1 cells were detected by flow cytometry. Immediately after 4 h of 40 microM arsenite treatment, no appreciable fraction of cells with sub-G1 DNA content was detected; however, the sub-G1 cell fraction increased with postarsenite incubation time, and detectable increase started at 8 h of incubation, whereas the intracellular peroxide level as measured by the fluorescent intensity of 2',7'-dichlorofluorescein increased immediately following a 4-h arsenite treatment. Simultaneous treatment with arsenite plus antioxidant (N-acetyl-cysteine, Trolox, and Tempo); copper ion chelator (neocuproine); protein kinase inhibitor (H-7) or protein synthesis inhibitor (cycloheximide) reduced the fraction of sub-G1 cell and internucleosomal DNA degradation. Trolox, neocuproine, or cycloheximide given after arsenite treatment also effectively reduced apoptosis. These results lead to a working hypothesis that arsenite-induced apoptosis in CHO-K1 cells is triggered by the generation of hydrogen peroxide, followed by a copper-mediated Fenton reaction that catalyzes the production of hydroxyl radicals, which selectively activates protein kinase through de novo synthesis of macromolecules.
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PMID:Arsenite induces apoptosis in Chinese hamster ovary cells by generation of reactive oxygen species. 890 93

Arsenic is a human carcinogen. On the other hand, selenium supplementation can inhibit induction of carcinogenesis by chemical carcinogens. The effect of selenium compounds on the cytotoxicity of dimethylarsinic acid (DMA) and on the induction of tetraploidy by DMA were studied using Chinese hamster V79 cells. Two selenium compounds were tested, sodium selenite and trimethylselenonium iodide (TMSeI). Trimethylselenonium is a major excretory product of selenite metabolism. The cytotoxicity of sodium selenite was 1000-fold greater than that of TMSeI. The cytotoxicity of DMA was about the same as that of TMSeI. The mitotic index for DMA administration was increased by these selenium compounds at low concentrations and decreased by them at high concentrations. The tetraploid index for DMA decreased with increasing concentrations of these selenium compounds. Tetraploidy is a form of aneuploidy, and aneuploidy is known to induce carcinogenesis. The finding that selenium inhibited induction of tetraploidy by DMA may yield clues to the role of selenium in the chemoprevention of carcinogenesis by chemical carcinogens.
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PMID:The inhibitory effect of selenium on induction of tetraploidy by dimethylarsinic acid in Chinese hamster cells. 921 48

Arsenic is a potent human carcinogen to which there is significant worldwide exposure through natural contamination of food and drinking water sources. Because arsenic is detoxified via methylation using a methyltransferase (MTase) and S-adenosylmethionine (SAM) as the methyl donor, we hypothesized that a mechanism of carcinogenesis of arsenic could involve alterations of MTase/SAM-dependent DNA methylation of a tumor suppressor gene. We found that exposure of human lung adenocarcinoma A549 cells to sodium arsenite (0.08-2 microM) or sodium arsenate (30-300 microM), but not dimethylarsenic acid (2-2000 microM), produced significant dose-responsive hypermethylation within a 341-base pair fragment of the promoter of p53. This was determined by quantitative PCR/HpaII restriction site analysis to analyze methylation status of two CCGG sites. In experiments with arsenite, DNA sequencing using bisulfite to visualize 5-methylcytosine (5-MeC) over the entire promoter region confirmed data obtained by restriction analysis. Limited data using SssI methylase also suggested that over-methylation of CpG sequences may exist over the entire genome in response to arsenite exposure. We propose that alteration of DNA methylation by arsenic offers a plausible, unified hypothesis for the carcinogenic mechanism of action of arsenic, and we present a model for arsenic carcinogenesis that utilizes perturbations of DNA methylation as the basis for the carcinogenic effects of arsenic.
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PMID:Arsenic alters cytosine methylation patterns of the promoter of the tumor suppressor gene p53 in human lung cells: a model for a mechanism of carcinogenesis. 921 64


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