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Titolo:
Benzo(a)pyrene diolepoxide adducts to albumin in workers exposed to polycyclic aromatic hydrocarbons: association with specific CYP1A1, GSTM1, GSTP1 and EHPX genotypes
Autore:
Pastorelli, R; Cerri, A; Rozio, M; DellOmo, M; Muzi, G; Abbritti, G; Fanelli, R; Airoldi, L;
Indirizzi:
Ist Ric Farmacol Mario Negri, Dept Environm Hlth Sci, I-20157 Milan, ItalyIst Ric Farmacol Mario Negri Milan Italy I-20157 i, I-20157 Milan, Italy Univ Perugia, Inst Occupat Med & Toxicol, I-06100 Perugia, Italy Univ Perugia Perugia Italy I-06100 Med & Toxicol, I-06100 Perugia, Italy
Titolo Testata:
BIOMARKERS
fascicolo: 5, volume: 6, anno: 2001,
pagine: 357 - 374
SICI:
1354-750X(200109)6:5<357:BDATAI>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
GLUTATHIONE-S-TRANSFERASE; MICROSOMAL EPOXIDE HYDROLASE; WHITE BLOOD-CELLS; COKE-OVEN WORKERS; LUNG-CANCER; DNA-ADDUCTS; GENETIC POLYMORPHISMS; FOUNDRY WORKERS; BENZOPYRENE DIOLEPOXIDE; POPULATION FREQUENCY;
Keywords:
benzo(a)pyrene diolepoxide adducts; occupational exposure; genetic polymorphism;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Pastorelli, R Ist Ric Farmacol Mario Negri, Dept Environm Hlth Sci, I-20157 Milan, Italy Ist Ric Farmacol Mario Negri Milan Italy I-20157 an, Italy
Citazione:
R. Pastorelli et al., "Benzo(a)pyrene diolepoxide adducts to albumin in workers exposed to polycyclic aromatic hydrocarbons: association with specific CYP1A1, GSTM1, GSTP1 and EHPX genotypes", BIOMARKERS, 6(5), 2001, pp. 357-374

Abstract

We investigated whether the presence of (+)-anti-benzo(a) pyrene diolepoxide adducts to serum albumin (BPDE-SA) among workers exposed to benzo( a) pyrene (BaP) and unexposed reference controls was influenced by genetic polymorphisms of cytochrome P4501A1 (CYP1A1), microsomal epoxide hydrolase (EHPX), glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), all involved in BaP metabolism. Exposed workers had significantly higher levels of adducts (0.124 +/- 0.02 fmol BPT mg(1) SA, mean +/- SE) and a higher proportion of detectable adducts (40.3%) than controls (0.051 +/- 0.01 fmol BPT mg(1) SA; 16.1%) ( p = 0.014 and p = 0.012). Smoking increased adduct levels only in occupationally exposed workers with the GSTM1 deletion (GSTM1 null) (p = 0.034). Smokers from the exposed group had higher adduct levels when they wereCYP1A1 *1/*1 wild-type rather than heterozygous and homozygous for the variant alleles (CYP1A1 *1/*2 plus *2/*2) ( p = 0.01). The dependence of BPDE-SA adduct levels and frequency on the CYP1A1 *1/*1 genotype was most pronounced in GSTM1-deficient smokers. Exposed workers with GSTM1 null/GSTP1 variant alleles had fewer detectable adducts than those with the GSTM1 null/GSTP1*A wild-type allele, supporting for the first time the recent in vitro finding that GSTP1 variants may be more effective in the detoxification of BPDE than the wild-type allele. Logistic regression analysis indicated that occupational exposure, wild-type CYP1A1*1/*1 allele and the combination of GSTM1 null genotype + EHPX genotypes associated with predicted low enzyme activity were significant predictors of BPDE-SA adducts. Though our findings should be viewed with caution because of the relatively limited size of thepopulation analysed, the interaction between these polymorphic enzymes andBPDE-SA adducts seems to be specific for high exposure and might have an impact on the quantitative risk estimates for exposure to polycyclic aromatic hydrocarbons.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/06/20 alle ore 00:02:29