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KMID : 0857020060210010284
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Kosin Medical Journal
2006 Volume.21 No. 1 p.284 ~ p.292
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Associations of the Genetic Polymorphisms of CYP2E1, GSTM1 and GSTT1 with Urinary Excretion of N-methylformamide in the Workers Exposed to N, N-dimethylformamide
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Kim Jae-Il
Lee Yong-Hwan
Lee Chung-Han
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Abstract
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Background: N,N-dimethylformamide (DMF) has excellent solvent properties and is used intensively in the production of synthetic leather and resins. It has known to induce hepatotoxicity in human and animal by absorbing it through the lungs and skin. The metabolic transformation of DMF takes place mainly in the liver, with the aid of microsomal enzyme systems including cytochrome P450 (CYP), and glutathione S-transferase (GST). In metabolic studies and biological monitoring, urinary concentrations of metabolites are measured and expressed as N-methylformamide (NMF). This study examined the associations of the genetic polmorphism of CYP2E1. GSTM1 and GSTT1 with DMF metabolism.
Methods: The subjects were 30 workers who exposed to DMF in a synthetic leather factory. Their urinary samples were collected and NMF concentrations were measured. Also, DMF concentrations in air were measured by personal air sampler during thier work. Genotypes of CYP2E1, GSTM1 and GSTT1 were investigated using PCR-RFLP or multiolex PCR methods with DNA extracted from venous blood. Effects of the polymorphisms of CYP2E1, GSTM1 and GSTT1 on DMF metabolism were analyzed.
Results: The frequency of c1/c1 and c1/c2 genotypes for CYP2E1 were 76.6% and 23.3%, respectively. GSTM1 was deleted in 53.3% and GSTT1 deletion rate was 40.0%. In the group of GSTM1 deletion, mean urinary NMF concentrations (95.2 mg/g creatinine) were significantly higher than the undeleted group (45.3 mg/g creatinine, p=0.042). There were no significant differences of mean urinary NMF concentrations in the groups with the defferent genotypes of CYP2E1 and GSTT1. The distribution of CYP2E1, GSTM1 and GSTT1 genotypes by urinary NMF concentrations had not statistical significance.
Conclusions: In GSTM1 deleted workers who exposed to DMF, mean urinary NMF concentration was higher than undeleted cases. GSTM1 deleted workers are seemed to be more susceptible to DMF toxicity. It is necessary to screen whether the workers have GSTM1 deleted genotype or not when they are arranged to their work place.
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KEYWORD
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N, N-dimethylformamide, N-methylformanide, CYP2E1, GSTM1, GSTT1
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