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Titolo:
Variant metabolizing gene alleles determine the genotoxicity of benzo[a]pyrene
Autore:
Salama, SA; Sierra-Torres, CH; Oh, HY; Hamada, FA; Au, WW;
Indirizzi:
Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77555 USA Univ Texas Galveston TX USA 77555 Community Hlth, Galveston, TX 77555 USA Al Azhar Univ, Fac Pharm, Dept Pharmacol & Toxicol, Cairo, Egypt Al Azhar Univ Cairo Egypt Pharm, Dept Pharmacol & Toxicol, Cairo, Egypt Korean Food & Drug Adm, Div Genet Toxicol, Natl Inst Toxicol Res, Seoul, South Korea Korean Food & Drug Adm Seoul South Korea oxicol Res, Seoul, South Korea
Titolo Testata:
ENVIRONMENTAL AND MOLECULAR MUTAGENESIS
fascicolo: 1, volume: 37, anno: 2001,
pagine: 17 - 26
SICI:
0893-6692(2001)37:1<17:VMGADT>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTATHIONE-S-TRANSFERASE; MICROSOMAL EPOXIDE HYDROLASE; INCREASED CHROMOSOME-ABERRATIONS; LUNG-CANCER RISK; CIGARETTE SMOKERS; 1CEN-1Q12 REGION; GSTT1 GENOTYPES; BLADDER-CANCER; DNA-ADDUCTS; M1 GSTM1;
Keywords:
genetic susceptibility; chromosome aberrations; genetic toxicology; polymorphic genes; chemical metabolism; carcinogenesis; toxicology;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
63
Recensione:
Indirizzi per estratti:
Indirizzo: Au, WW Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, 700 Harborside Dr, Galveston, TX 77555 USA Univ Texas 700 Harborside Dr Galveston TX USA 77555 n, TX 77555 USA
Citazione:
S.A. Salama et al., "Variant metabolizing gene alleles determine the genotoxicity of benzo[a]pyrene", ENV MOL MUT, 37(1), 2001, pp. 17-26

Abstract

Understanding the mechanisms involved with genetic susceptibility to environmental disease is of major interest to the scientific community. We have conducted an in vitro study to elucidate the involvement of polymorphic metabolizing genes on the genotoxicity of benzo[a]pyrene (BP). Blood samples from 38 donors were treated with BP and the induction of sister chromatid exchanges (SCE) and chromosome aberrations (CA) were evaluated. The latter isbased on the tandem-probe fluorescence in situ hybridization (FISH) assay. The data indicate that the induction of genotoxicity was clearly determined by the inherited variant genotypes For glutathione-S-transferase (GSTM1) and microsomal epoxide hydrolase (EH). In a comparison of the two biomarkers, the CA biomarker shows a more definite association with the genotypes than does SCE. For example, the presence of the GSTM1 null genotype (GSTM1 0/0) is responsible for the highest level and significant induction of CA, irrespective of the presence of other genotypes in the different donors. Thiseffect is further enhanced significantly by the presence of the excessive activation EH gene allele (EH4*) and decreased by the reduced activation EHgene allele (EH3*). Overall, the modulation of genotoxicity by the susceptibility genotypes provides support of their potential involvement in environmental cancer. Furthermore, the data indicate that the variant enzymes function independently by contributing their metabolic capability toward the expression of biologic activities. Therefore, studies like this one can be used to resolve the complexity of genetic susceptibility to environmental disease in human. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/09/20 alle ore 01:08:29