CYP2E1與GST基因多型性對二甲基甲醯胺職業暴露之生物指標之影響

Effects of Genetic Polymorphism of CYP2E1 and GST on Urinary Biomarkers of Occupational Exposure to N, N-dimethylformamide

本研究目的是探討職業暴露二甲基甲醯胺（N,N-dimethylformamide, DMF）之作業勞工體內 CYP2E1及GST不同基因型（genotypes）對DMF尿液中DMF、 NMF及AMCC三種生物指標物的影響。本研究選取某合成皮製造廠 49 位男性作業員工，進行全程勞工個人 DMF 暴露測定，並收集勞工下班後的尿液進行尿中 DMF、 NMF 及 AMCC 的分析，及進行勞工體內 CYP2E1 （Pst1 及 Dra1）及 GST （T1/ M1）基因多型性的分析。空氣 DMF 暴露濃度（ppm）及尿中 DMF、NMF 及 AMCC 濃度（mg/L）平均值為 7.59、0.76、9.36 及 15.29。本研究發現 CYP2E1 之基因型和三種 DMF 尿中指標物皆未呈現顯著相關，而尿中 AMCC 濃度除受到空氣中 DMF 暴露值影響外，尚受到受測者體內 GSTT1 及 GSTM1 之基因型分布之影響，建議以尿中 AMCC 作為 DMF 職業暴露之內在指標時，應考量 GST 之基因多型性，方不致對 DMF 暴露產生錯估。

The purpose of this study is to investigate the effects of genetic polymorphism of CYP2E1 and GST on three urinary biomarkers of N, N-dimethylformamide (DMF) exposure. Forty-nine male workers in a synthetic leather factory were environmentally monitored on their full work-shift exposure to DMF. DMF, N-methylformamide (NMF) and N-acetyl-S-(N-methylcarbamoyl) cysteine (AMCC) in urine were collected and analyzed immediately after the shift change. Their genetic polymorphism of CYP2E1 (Pst1 and Dra1), and GST (T1 and M1) was determined by PCR (Polymerase Chain Reaction) and RFLP (Restriction fragment length polymorphism) from the peripheral lymphocytes. It was found the average concentrations of DMF in the air and DMF, NMF, and AMCC in urine were 7.59 ppm, 0.76, 9.36, and 15.29 mg/L, respectively. No biomarkers in urine presented association with the CYP2E1 variants. Urinary AMCC, however, revealed significant association with the variants of both GSTT1 and GSTM1 after adjustment for DMF concentrations in the air. It is suggested that the use of urinary AMCC as a biomarker of DMF exposure should take the GST variants into account to avoid erroneous exposure estimates.