Individual sensitivity to DNA damage induced by styrene in vitro:: influence of cytochrome P450, epoxide hydrolase and glutathione S-transferase genotypes

被引:34
作者
Laffon, B
Pérez-Cadahía, B
Pásaro, E
Méndez, J
机构
[1] Univ A Coruna, Fac Ciencias, Dept Biol Celular & Mol, La Coruna 15071, Spain
[2] Univ A Coruna, Inst Ciencias Salud, La Coruna 15071, Spain
关键词
styrene; comet assay; genetic polymorphisms; cytochrome P450; epoxide hydrolase; glutathione S-transferase;
D O I
10.1016/S0300-483X(02)00729-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Styrene is a monomer of great commercial interest; its polymers and copolymers are used in a wide range of applications. In humans, styrene metabolism involves oxidation by cytochrome P450 monooxygenases (CYPs) to styrene-7,8-oxide, an epoxide thought to be responsible for the genotoxic effects of styrene exposure and detoxification by means of epoxide hydrolase (EH) and glutathione S-transferases (GSTs). The objective of this study was to investigate if genetic polymorphisms of metabolic enzymes modulate styrene-induced DNA damage in human leukocytes. CYP2E1, CYP1A1, EH, GSTP1, GSTM1 and GSTT1 polymorphisms were determined in 30 healthy donors and alkaline comet assay was carried out in isolated leukocytes exposed to 5 and 10 mM styrene, using 1% acetone as solvent control. The results obtained suggest that CYP1A1 m1, m2 and m4, CYP2E1 Dra I and GSTP1 (exons 5 and 6) polymorphisms may affect styrene induction of DNA damage in human leukocytes. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
引用
收藏
页码:131 / 141
页数:11
相关论文
共 51 条
[1]  
AliOsman F, 1997, J BIOL CHEM, V272, P10004
[2]   Genetic polymorphisms in human xenobiotica metabolizing enzymes as susceptibility factors in toxic response [J].
Autrup, H .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2000, 464 (01) :65-76
[3]   Influence of GSTM1 and GSTT1 genotypes on sister chromatid exchange induction by styrene in cultured human lymphocytes [J].
Bernardini, S ;
Hirvonen, A ;
Järventaus, H ;
Norppa, H .
CARCINOGENESIS, 2002, 23 (05) :893-897
[4]   MICROGEL ELECTROPHORESIS ASSAY (COMET TEST) AND SCE ANALYSIS IN HUMAN-LYMPHOCYTES FROM 100 NORMAL SUBJECTS [J].
BETTI, C ;
DAVINI, T ;
GIANNESSI, L ;
LOPRIENO, N ;
BARALE, R .
MUTATION RESEARCH, 1994, 307 (01) :323-333
[5]   Analyses of bulky DNA adduct levels in human breast tissue and genetic polymorphisms of cytochromes P450 (CYPs), myeloperoxidase (MPO), quinone oxidoreductase (NQO1), and glutathione S-transferases (GSTs) [J].
Brockstedt, U ;
Krajinovic, M ;
Richer, C ;
Mathonnet, G ;
Sinnett, D ;
Pfau, W ;
Labuda, D .
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS, 2002, 516 (1-2) :41-47
[6]   Human cytochrome P450 2E1 (CYP2E1): From genotype to phenotype [J].
Carriere, V ;
Berthou, F ;
Baird, S ;
Belloc, C ;
Beaune, P ;
deWaziers, I .
PHARMACOGENETICS, 1996, 6 (03) :203-211
[7]  
Cascorbi I, 1996, CANCER RES, V56, P4965
[8]   The HUman MicroNucleus Project - An international collaborative study on the use of the micronucleus technique for measuring DNA damage in humans [J].
Fenech, M ;
Holland, N ;
Chang, WP ;
Zeiger, E ;
Bonassi, S .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1999, 428 (1-2) :271-283
[9]   THE CYTOKINESIS-BLOCK MICRONUCLEUS TECHNIQUE - A DETAILED DESCRIPTION OF THE METHOD AND ITS APPLICATION TO GENOTOXICITY STUDIES IN HUMAN-POPULATIONS [J].
FENECH, M .
MUTATION RESEARCH, 1993, 285 (01) :35-44
[10]  
Ghittori S, 1997, AM J IND MED, V31, P636, DOI 10.1002/(SICI)1097-0274(199705)31:5<636::AID-AJIM20>3.0.CO