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Titolo:
DNA adducts: effects of low exposure to ethylene oxide, vinyl chloride andbutadiene
Autore:
Swenberg, JA; Ham, A; Koc, H; Morinello, E; Ranasinghe, A; Tretyakova, N; Upton, PB; Wu, KY;
Indirizzi:
Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 Engn, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Pathol, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 athol, Chapel Hill, NC 27599 USA Univ N Carolina, Dept Toxicol, Chapel Hill, NC 27599 USA Univ N Carolina Chapel Hill NC USA 27599 xicol, Chapel Hill, NC 27599 USA
Titolo Testata:
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
fascicolo: 1, volume: 464, anno: 2000,
pagine: 77 - 86
SICI:
1383-5718(20000103)464:1<77:DAEOLE>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
CALF THYMUS DNA; HERITABLE TRANSLOCATIONS; LIVER DNA; IN-VIVO; RATS; N2,3-ETHENOGUANINE; 7-(2-HYDROXYETHYL)GUANINE; 3,4-EPOXY-1-BUTENE; CARCINOGENESIS; 1,3-BUTADIENE;
Keywords:
ethylene oxide; vinyl chloride; butadiene; DNA adducts; molecular dose; low dose; risk assessment; occupational exposure;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
45
Recensione:
Indirizzi per estratti:
Indirizzo: Swenberg, JA Univ N Carolina, Dept Environm Sci & Engn, Campus Box 7400, Chapel Hill, NC 27599 USA Univ N Carolina Campus Box 7400 Chapel Hill NC USA27599 USA
Citazione:
J.A. Swenberg et al., "DNA adducts: effects of low exposure to ethylene oxide, vinyl chloride andbutadiene", MUT RES-GTE, 464(1), 2000, pp. 77-86

Abstract

Dose-response relationships of genotoxic agents differ greatly depending on the agent and the endpoint being evaluated. Simple conclusions that genotoxic effects are linear cannot be applied universally. The shape of the molecular dose of DNA adducts varies from linear, to supralinear, to sublineardepending on metabolic activation and detoxication, and repair of individual types of DNA adducts. For mutagenesis and other genotoxicity endpoints, the dose-response reflects the molecular dose of each type of DNA adduct, cell proliferation, as well as endogenous factors that lead to mutagenesis such as the formation and repair of endogenous DNA adducts. These same factors are important when interpreting the shape of dose-response data for carcinogenesis of genotoxic agents, however, tumor background variability adds additional complexity. Endogenously formed DNA adducts may be identical to those formed by chemicals, as in the case of vinyl chloride and ethylene oxide, or they may be those associated with oxidative stress. Data presented in this paper demonstrate that the exogenous number of adducts induced by 5days of exposure to 10 ppm vinyl chloride is only 2.2-fold greater than that present as a steady-state amount in unexposed control rats. Similar dataare shown for ethylene oxide. Extremely sensitive methods have been developed for measuring the molecular dose of genotoxins. These methods can detect DNA adducts as low as 1 per 10(9) to 10(10). However, in view of the highnumber of endogenous DNA adducts that are present in all cells, it is unlikely that causal relationships can be attributed to very low numbers of such DNA adducts. Effects of both exogenous and endogenous DNA adducts need tobe factored into the interpretation of chemical exposures. (C) 2000 Elsevier Science B.V. All rights reserved.

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Documento generato il 13/07/20 alle ore 06:19:36