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

Cancer etiology involves the interplay of genetic and environmental factors. Striking geographic differences and changes in cancer incidence over time have led epidemiologists to infer that probably the major etiologic component is environmental. Recent experiences with vinyl chloride, kepone, and polybrominated biphenyl illustrate the problems involved in epidemiologic studies of proven or suspected environmental carcinogens. While epidemiologic studies will continue to be an essential means for monitoring potential human risks, the long latent periods involved in human carcinogenesis severely limit the usefulness of such approaches for disease prevention. While in vitro and animal test systems can never fully supplant human studies, they represent our only means for detecting potential carcinogenicity before human exposure has become widespread or long established.
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PMID:Environmental pollutants and the epidemiology of cancer. 8 37

One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of "no-adverse-effect-levels". Arguments in favour of the postulated "irreversibility" of carcinogenic effects are based on dose-response studies, single-dose and multi-generation experiments as well as on the concept of somatic mutation as the first steps in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero-tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes never should be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available. Several systems of short-term tests as screening methods are based on mutagenicity tests and offer many advantages. Their critical evaluation is of utmost importance. Examples of some relevant problems to be discussed include nitrosamines in food products and their formation from ingested precursors; the migration of vinyl chloride from PVC food packing material; the occurrence of low levels of chloroform in drinking water.
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PMID:Toxicological aspects of food safety - carcinogenicity and mutagenicity. 35 95

New aspects on the mechanism of action of known environmental carcinogens are described. These compounds are not active as such, but are bioactivated in the mammalian metabolism via chemically reactive intermediates to electrophilic reactants, forming with information-bearing biopolymeres covalent bonds. This change in the genetic code is in agreement with the mutation hypothesis of carcinogenesis. Aflatoxin B1, N-nitroso compounds and benzo(a)pyrene are taken as examples. "Threshold levels", e.g. no-effect-levels derived from animal experiments with all their inherent limitations, are compared with data from human exposure to benzo(a)pyren, aflatoxine, N-nitroso compounds and vinyl chloride. The difficulties of such risk evaluations are discussed.
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PMID:[Environmental carcinogens: mechanisms of action and occurrence. Some aspects (author's transl)]. 41 5

Clues to causes of cancer in man can be identified through clinical observation of patients. Alert practitioners have, for example, recently discovered carcinogenic effects of occupational exposure to vinyl chloride and of diethylstilbestrol therapy during gestation. Clinical case studies have also clarified the role of host susceptibility in development of cancer. In most instances, validity of initial clinical observations was established by more detailed epidemiologic and laboratory studies. Clinicians can contribute to carcinogenesis studies by being alert to causes of cancer in their patients, and by referring exceptional observations to clinical epidemiologists and basic scientists for further study. Knowledge of risk factors can be applied to cancer prevention and early detection.
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PMID:Clinical studies of cancer etiology. 56 Feb 47

Poly(vinyl chloride) (PVC) is a complex plastic system. Individual components of the PVC system, including residual vinyl chloride monomer (RVCM) and certain additives, may pose risks of harm to human health. There have been significant reductions in the RVCM content of PVC resin since 1974, reducing the cancer risk of workers in PVC fabrication plants and consumers of PVC products. A "no-effect" level for vinyl chloride monomer (VCM)-induced carcinogenesis has not been found to date; therefore, the significance of human exposure to low levels of RVCM remains to be determined. Exposure to PVC dust may cause pulmonary dysfunctions. Pulmonary and other possible health effects of PVC dust require further study. The PVC plastics system should be characterized as to interactions among its various components and as to interactions of the components and the PVC system as a whole with biological systems.
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PMID:PVC: health implications and production trends. 79 61

Mutagenicity tester strains of Bacillus and Salmonella were used to assay vinyl chloride in nutrient broth at a practical concentration level. Also screened without exogenous activation were seven potential metabolites of vinyl chloride in their pure forms as well as the related epichlorohydrin. Chlorooxirane, chloroacetaldehyde, chloroacetaldehyde monomer hydrate, chloroacetaldehyde dimer hydrate, chloroacetaldehyde trimer, and epichlorohydrin produced significant mutagenic acitivity in Salmonella typhimurium strains sensitive to base-pair mutation. A recombination repair deficient strain of Bacillus subtilis was inhibited in growth by these compounds, whereas excision repair deficient and wild type strains of Bacillus subtilis were relatively unaffected. On the basis of these assays a working hypothesis for the vinyl chloride carcinogenesis mechanism is proposed which involves chlorooxirane and chloroacetaldehyde monomer hydrate as the ultimate carcinogenic metabolites of vinyl chloride.
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PMID:Vinyl chloride mutagenicity via the metabolites chlorooxirane and chloroacetaldehyde monomer hydrate. 82 75

A patient with hemangiopericytoma of the bladder following intensive exposure to polyvinyl alcohol is reported. Some early studies on polymer carcinogenesis are reviewed and recent work on vinyl chloride as a mutagen and potent carcinogen is cited. The need for epidemiologic and animal studies of other monomers is presented.
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PMID:Hemangiopericytoma of the bladder after polyvinyl alcohol exposure. 91 62

There is need for a new active approach to the problem of occupational carcinogenesis. It is no longer acceptable to adopt a "wait and see" attitude since: 1. evidence suggests that cancer is an "ecological" disease; 2. The carcinogenic risk has been increasing as industrialisation increased; 3. Factory workers are the most exposed population and hazards spread from the work-place to the general population as consumer goods and pollution. It is necessary and possible, to identify potential carcinogens before workers and the general population are exposed. That predictive experiments could be done, is exemplified by the history of stilboestrol, bis (chloromethyl) ether, vinyl chloride and chromium pigments, all of which were reported carcinogenic in animal tests before any epidemiological results were available. Unforturnately, these results were received with scepticism because the test methods were thought to be inadequate. It is necessary to develop the future policy of prevention by: 1. establishing a priority for testing compounds already produced and widespread in occurence and those about to be produced on a large scale; 2. establishing experimental models for determining carcinogenic risk, especially rapid screening tests; 3. study of the more important compounds by long-term bioassays. Full details are given of the testing of vinyl chloride monamer and preliminary results are tabulated for tests on styrene, acrylonitrile and vinylidene chloride.
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PMID:Occupational chemical carcinogenesis: new facts, priorities and perspectives. 100 72

Trichloroethylene (TCE), a structural analog of vinyl chloride, is known to induce hepatocellular carcinoma and other tumors in C57BL/6 X C3H/He F1 (hereafter known as B6C3F1) hybrid mice. TCE epoxide, a possible metabolite, is expected to be highly reactive toward cellular nucleophiles, e.g., proteins and nucleic acids. Hence, the microsomal metabolism of TCE and its covalent binding to microsomal protein were examined. Rat liver microsomes were incubated in vitro with [14C]TCE. The results showed that TCE binds covalently to microsomal protein since extensive organic extractions and Pronase digestion do not dissociate the TCE-protein complex. The binding was decreased by 7,8-benzoflavone, blocked by SKF-525A, and enhanced by i.p. administration of phenobarbital. The possibility that TCE epoxide, once formed, could be converted to water-soluble products through enzymatic hydrolysis by epoxide hydrase was also investigated. Addition of 3,3,3-trichloropropene oxide, a potent inhibitor of epoxide hydrase, to the incubation system markedly enhanced the binding of TCE. These observations support the view that, in order to bind to protein, it is necessary for TCE to be metabolized to its epoxide, a reactive intermediate that is most likely involved in TCE carcinogenesis and toxicity.
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PMID:Covalent interaction of metabolites of the carcinogen trichloroethylene in rat hepatic microsomes. 127 48

Chromosome aberration assays, sister-chromatid exchange techniques and micronucleus assays are commonly used methods for biomonitoring genetic material damaged by chemical or physical agents. On the other hand, their aneugenic activity, which can lead to hypoploidy and may also be associated with carcinogenesis, has not been thoroughly investigated. In our study we chose the micronucleus assay with a new mathematical approach to separate clastogenic from aneugenic activity of three well-known mutagens (vinyl chloride monomer, X-rays and microwaves) on the genome of human somatic cells. The comparison of frequencies of size distribution of micronuclei in the lymphocytes of humans exposed to each of these three mutagens showed that X-rays and microwaves were preferentially clastogens while vinyl chloride monomer showed aneugenic activity as well. Microwaves possess some mutagenic characteristics typical of chemical mutagens.
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PMID:X-rays, microwaves and vinyl chloride monomer: their clastogenic and aneugenic activity, using the micronucleus assay on human lymphocytes. 137 89


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