Influence of genetic polymorphisms of styrene-metabolizing enzymes and smoking habits on levels of urinary metabolites after occupational exposure to styrene

Here we evaluate the influence of individual genetic polymorphisms of drug-metabolizing enzymes as well as body mass index (BMI) and lifestyle (smoking, alcohol consumption) on urinary metabolites after occupational exposure to styrene. Seventy-three workers exposed to styrene in a reinforced-plasti...

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Veröffentlicht in:Toxicology letters 2005-12, Vol.160 (1), p.84-91
Hauptverfasser: Ma, Mingyue, Umemura, Tomohiro, Mori, Yuko, Gong, Yingyan, Saijo, Yasuaki, Sata, Fumihiro, Kawai, Toshio, Kishi, Reiko
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container_end_page 91
container_issue 1
container_start_page 84
container_title Toxicology letters
container_volume 160
creator Ma, Mingyue
Umemura, Tomohiro
Mori, Yuko
Gong, Yingyan
Saijo, Yasuaki
Sata, Fumihiro
Kawai, Toshio
Kishi, Reiko
description Here we evaluate the influence of individual genetic polymorphisms of drug-metabolizing enzymes as well as body mass index (BMI) and lifestyle (smoking, alcohol consumption) on urinary metabolites after occupational exposure to styrene. Seventy-three workers exposed to styrene in a reinforced-plastics workplace were studied. The personal styrene exposure in the air and the urinary styrene metabolites mandelic acid and phenylglyoxylic acid were measured. The subjects’ genetic polymorphisms in the genes that encode the styrene-metabolizing enzymes CYP2E1, CYP2B6, EPHX1, GSTM1, GSTT1 and GSTP1 were determined. Neither genotype nor lifestyle significantly affected urinary metabolites. There was, however, an interaction between the CYP2E1 genotype and smoking. Among non-smokers, urinary styrene metabolites were significantly decreased in subjects with c1/c1 alleles of CYP2E1 as compared with those with the c1/c2 genotype. There was no significant difference in urinary metabolites among smokers. When the combined influence of the CYP2B6 genotype and the predicted activity of EPHX1 were examined, urinary metabolites in subjects with low enzyme activity were lower than in those with medium or high activity after high styrene exposure (≥50 ppm). The results suggest that genetic susceptibility and lifestyle should be considered in biological monitoring of exposure to styrene.
doi_str_mv 10.1016/j.toxlet.2005.06.011
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Seventy-three workers exposed to styrene in a reinforced-plastics workplace were studied. The personal styrene exposure in the air and the urinary styrene metabolites mandelic acid and phenylglyoxylic acid were measured. The subjects’ genetic polymorphisms in the genes that encode the styrene-metabolizing enzymes CYP2E1, CYP2B6, EPHX1, GSTM1, GSTT1 and GSTP1 were determined. Neither genotype nor lifestyle significantly affected urinary metabolites. There was, however, an interaction between the CYP2E1 genotype and smoking. Among non-smokers, urinary styrene metabolites were significantly decreased in subjects with c1/c1 alleles of CYP2E1 as compared with those with the c1/c2 genotype. There was no significant difference in urinary metabolites among smokers. When the combined influence of the CYP2B6 genotype and the predicted activity of EPHX1 were examined, urinary metabolites in subjects with low enzyme activity were lower than in those with medium or high activity after high styrene exposure (≥50 ppm). The results suggest that genetic susceptibility and lifestyle should be considered in biological monitoring of exposure to styrene.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>16125881</pmid><doi>10.1016/j.toxlet.2005.06.011</doi><tpages>8</tpages></addata></record>
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subjects Adult
Alcohol Drinking - urine
Aryl Hydrocarbon Hydroxylases - genetics
Aryl Hydrocarbon Hydroxylases - metabolism
Biological and medical sciences
Biological monitoring
Body Mass Index
Chemical and industrial products toxicology. Toxic occupational diseases
Cytochrome P-450 CYP2B6
Cytochrome P-450 CYP2E1 - genetics
Cytochrome P-450 CYP2E1 - metabolism
Epoxide Hydrolases - genetics
Epoxide Hydrolases - metabolism
Genetic polymorphisms
Genotype
Glutathione S-Transferase pi - genetics
Glutathione S-Transferase pi - metabolism
Glutathione Transferase - genetics
Glutathione Transferase - metabolism
Glyoxylates - urine
Humans
Male
Mandelic acid (MA)
Mandelic Acids - urine
Medical sciences
Occupational Exposure - adverse effects
Oxidoreductases, N-Demethylating - genetics
Oxidoreductases, N-Demethylating - metabolism
Phenylglyoxylic acid (PGA)
Polymerase Chain Reaction
Polymorphism, Genetic
Smoking - urine
Solvents
Styrene
Styrene - metabolism
Styrene - poisoning
Tobacco, tobacco smoking
Toxicology
title Influence of genetic polymorphisms of styrene-metabolizing enzymes and smoking habits on levels of urinary metabolites after occupational exposure to styrene
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