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Titolo:
Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure
Autore:
Schoket, B; Papp, G; Levay, K; Mrackova, G; Kadlubar, FF; Vincze, I;
Indirizzi:
Jozef Fodor Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Dept Biochem, H-1097 Budapest, Hungary Jozef Fodor Natl Ctr Publ Hlth Budapest Hungary H-1097 Budapest, Hungary Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA Natl Ctr Toxicol Res Jefferson AR USA 72079 miol, Jefferson, AR 72079 USA
Titolo Testata:
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
fascicolo: 1-2, volume: 482, anno: 2001,
pagine: 57 - 69
SICI:
1386-1964(20011001)482:1-2<57:IOMGOL>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA ADDUCT LEVELS; COKE-OVEN WORKERS; S-TRANSFERASE M1; WHITE BLOOD-CELLS; AMBIENT AIR-POLLUTION; HPRT MUTANT FREQUENCY; CYTOCHROME-P450 1A1; NAT2 GENOTYPES; LUNG-CANCER; GLUTATHIONE TRANSFERASES;
Keywords:
genetic polymorphism; metabolic genotype; molecular epidemiology; polycyclic aromatic hydrocarbons; biomarker; genotoxic exposure; DNA adduct; 1-hydroxypyrene;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
62
Recensione:
Indirizzi per estratti:
Indirizzo: Schoket, B Jozef Fodor Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Dept Biochem, H-1097 Budapest, Hungary Jozef Fodor Natl Ctr Publ Hlth Budapest Hungary H-1097 ungary
Citazione:
B. Schoket et al., "Impact of metabolic genotypes on levels of biomarkers of genotoxic exposure", MUT RES-F M, 482(1-2), 2001, pp. 57-69

Abstract

Phase I and Phase II xenobiotic-metabolising enzyme families are involved in the metabolic activation and detoxification of various classes of environmental carcinogens. Particular genetic polymorphisms of these enzymes havebeen shown to influence individual cancer risk. A brief overview is presented about recent research of the relationship between metabolic genotypes and internal dose, biologically effective dose and cytogenetic effects of complex and specific genotoxic exposures of human study populations, and we report our new results from two molecular epidemiological studies. We investigated the effects of multiple interactions among CYP1A1 Ile462Val CYP1A1 MspI, CYP1B1 Leu432Val, CYP2C9 Arg144Cys, CYP2C9 Ile359Leu, NQO1 Pro189Ser, GSTM1 gene deletion and GSTP1 Ile105Val genotypes on the levels of carcinogen-DNA adducts determined by P-32-postlabelling and PAH-DNA immunoassay in peripheral blood lymphocytes from workers occupationally exposed to polycyclic aromatic hydrocarbons in aluminium plants, and in bronchial tissue fromsmoking lung patients. A statistically significant positive linear correlation was observed between white blood cell aromatic DNA adduct and urinary 1-hydroxypyrene (1-OHPY) levels from potroom workers with GSTM1 null genotype (P = 0.011). Our results suggest interactions between GSTM1 and GSTP1 alleles in modulation of urinary 1-OHPY levels and white blood cell DNA adduct levels in the PAH-exposed workers. Interactions between GSTM1 and GSTP1 alleles, in association with particular genotype combinations of CYPs, were also recognised in bronchial aromatic DNA adduct levels of smoking lung patients, The impact of single metabolic genotypes and their combinations on biomarkers of exposure was usually weak, if any, in both our studies and reports of the literature. The effect of special metabolic gene interactions may be better recognised if the compared groups of individuals are stratified for multiple potential modulators of the observable biomarker end-point, and/or if chemical structure-specific biomarker methods are applied. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/04/20 alle ore 07:15:05