THE GST T1 AND CYP2E1 GENOTYPES ARE POSSIBLE FACTORS CAUSING VINYL-CHLORIDE INDUCED ABNORMAL LIVER-FUNCTION

Citation
Cy. Huang et al., THE GST T1 AND CYP2E1 GENOTYPES ARE POSSIBLE FACTORS CAUSING VINYL-CHLORIDE INDUCED ABNORMAL LIVER-FUNCTION, Archives of toxicology, 71(8), 1997, pp. 482-488
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Toxicology
Journal title
ISSN journal
0340-5761
Volume
71
Issue
8
Year of publication
1997
Pages
482 - 488
Database
ISI
SICI code
0340-5761(1997)71:8<482:TGTACG>2.0.ZU;2-U
Abstract
Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans, There are reports that exposure to VCM seems to induce abnorm al liver function, liver fibrosis, cirrhosis, portal hypertension, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form the electrophilic metabolites, chloroethylen e oxide (CEO) and chloroacetaldehyde (CAA), which may either cause cel l damage or be further metabolized and detoxified by glutathione S-tra nsferases (GSTs). This study investigated whether or not the genotypes CYP2E1, glutathione S-transferase theta (GST T1) and mu (GST M1) corr elated with abnormal liver function found in vinyl chloride exposed wo rkers, For this study, 251 workers from five polyvinyl chloride plants were enrolled. The workers were classified into two exposure groups ( high and low) and the degree of exposure was determined based on their job titles and airborne VCM concentration. The activity of serum alan ine aminotransferase (ALT) was used as the parameter of liver function . The genotypes CYP2E1, GST T1 and GST M1 were determined by polymeras e chain reaction and restriction fragment, length polymorphism on peri pheral white blood cell DNA. Other potential risk factors were also as certained and the confounding effect was adjusted accordingly. Stratif ied analyses were used to explore the correlation between the alterati on of liver function and the genotypes CYP2E1. GST T1 and GST M1 among the workers exposed to different levels of VCM. The following results were obtained (1) at low VCM exposure, the odds ratio (OR) of positiv e GST T1 on abnormal ALT was 3.8 (95% CI 1.2-14.5) but the CYP2E1 geno type was not associated with abnormal ALT. (2) At high VCM exposure, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR 5.4, 95% CI 0.7-35.1) and positive GST T1 was significantly assoc iated with decreased OR on abnormal ALT (OR 0.3, 95% CI 0.1-0.9). (3) Multiple linear and logistic regression also showed strong interaction s of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. The se observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, the effect of w hich leads to liver damage.