- Full (HTML) - Full (PDF) - Related EHP Articles - PubMed:Related Articles - PubMed:Citation - Cited in PMC - Purchase This Issue

Junxiang Wan,^1,* Jinxiu Shi,^2,* Lijian Hui,^2,* Dan Wu,² Xipeng Jin,¹ Naiqing Zhao,³ Wei Huang,⁴ Zhaolin Xia,¹ and Gengxi Hu²

¹Department of Occupational and Environmental Health, School of Public Health, Fudan University, Shanghai, China; ²Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai, China; ³Department of Statistics, School of Public Health, Fudan University, Shanghai, China; ⁴Shanghai Human Genome Center, Shanghai, China

Abstract

Metabolic enzymes involved in benzene activation or detoxification, including NAD(P) H, quinone oxidoreductase 1 (NQO1) , cytochrome P450 2E1 (CYP2E1) , myeloperoxidase (MPO) , glutathione-S-transferase mu-1 (GSTM1) , and glutathione-S-transferase theta-1 (GSTT1) , were studied for their roles in human susceptibility to benzene poisoning. The potential interactions of these metabolic enzymes with lifestyle factors such as cigarette smoking and alcohol consumption were also explored. We studied 156 benzene-poisoning patients and 152 workers occupationally exposed to benzene in South China. Sequencing, denaturing HPLC, restriction fragment-length polymorphism, and polymerase chain reaction were used to detect polymorphisms on the promoters and complete coding regions of NQO1, CYP2E1, MPO, and the null genotypes of GSTM1 and GSTT1. Seventeen single nucleotide polymorphisms (SNPs) were identified in NQO1, CYP2E1, and MPO genes, including 6 novel SNPs in CYP2E1 and MPO. Of the subjects who smoked and drank alcohol, an 8.15-fold [95% confidence interval (CI) , 1.43-46.50] and a 21.50-fold (95% CI, 2.79-165.79) increased risk of benzene poisoning, respectively, were observed among the subjects with two copies of NQO1 with a C-to-T substitution in cDNA at nucleotide 609 (c.609 C>T variation ; i.e., NQO1 c.609 T/T) compared to those with the heterozygous or wild (NQO1 c.609 C/T and c.609 C/C) genotypes. Our data also indicated that individuals with CYP2E1 c.-1293 C/C and c.-1293 G/C, and NQO1 c.609 T/T, and GSTT1 null genotypes tended to be more susceptible to benzene toxicity. Our results suggest that the combined effect of polymorphisms in NQO1, CYP2E1, and GSTT1 genes and lifestyle factors might contribute to benzene poisoning. Key words: benzene poisoning, polymorphisms, lifestyle, NQO1, CYP2E1, MPO, GSTM1, GSTT1. Environ Health Perspect 110:1213-1218 (2002) . [Online 15 October 2002]

http://ehpnet1.niehs.nih.gov/docs/2002/110p1213-1218wan/abstract.html

Address correspondence to G. Hu, Institute of Biochemistry and Cell Biology, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, 320 Yue-yang Road, Shanghai 200031, China. Telephone: 86-21-64378218. Fax: 86-21-64378218. E-mail: xbshu@sunm.shcnc.ac.cn

You may also address correspondence to Z. Xia, Department of Occupational and Environmental Health, School of Public Health, Fudan University, 138 Yi-xueyuan Road, Shanghai 200032, China. Telephone: 86-21-64041900-2196. Fax: 86-21-64037260. E-mail: zlxia@shmu.edu.cn

*These authors contributed equally to this work.

We thank D. Cao, J. Guan, X. Gao, and W. Liu.

This study was supported by an institutional review board of the Chinese Academy of Sciences and Ministry of Health (grants 970231006 and 96Q030, respectively) .

This study was supported by an institutional review board of the Chinese Academy of Sciences and Ministry of Health (grants 970231006 and 96Q030, respectively) . This work was part of project 30271113 supported by the National Natural Science Foundation of China. This work was part of project 30271113 supported by the National Natural Science Foundation of China.

Received 7 February 2002 ; accepted 26 April 2002.