Effects of Genotyping and Phenotyping of Cytochrome P4502E1 and Glutathione-S-transferase on the Biological Monitoring of Workers with Occupational Exposure to N,N-dimethylformamide

• Main Authors: Yu-Ching Chiu, 邱幼青
• Other Authors: Jyun-De Wu
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/32446917166457896334

碩士 === 長榮大學 === 職業安全與衛生研究所 === 95 === The merabolism of N,N-dimethylformamide （DMF） in a human body involves cytochrome P450 2E1 （CYP2E1） and glutathione-S-transferase （GST）. It has been known that these two enzymes own different kinds of genetic polymorphisms. The different genetic polymorphisms of the enzymes make the expressions of the enzyme activities for the metabolism of DMF and the health effects cause by DMF in humans become very different. The objectives of this study are: （1） to investigate the effects of genetic polymorphisms of CYP2E1 and GST on three urinary biomarkers, i.e., N-methylformamide （NMF）, DMF and N-acetyl-S-（N-methylcarbamoyl）cysteine （AMCC）, of DMF exposure; （2） to compare the difference of liver function between workers with and without DMF exposure and to explore the association between genetic polymorphisms and activity expressions of the DMF metabolic enzymes. One hundred and six workers （including 49 workers with DMF exposure and 57 workers without DMF exposure） were recruited in this study. For the workers with DMF exposure, personal full-shift airborne exposure, urine and blood samples were collected. For the workers without DMF exposure, urine and blood samples were collected. Passive samples （3M 3500） were used to measure the personal DMF airborne exposure. The collection of urine samples for the DMF exposed workers was conducted during work shift and in 24 hours after the end of the work shift. The samples of airborne exposure were analyzed by GC/FID （HP-5890）. The amounts of DMF and NMF in the urine samples were measured by GC/NPD （Varian 3600）. The amount of AMCC in the urine samples were measured by HPLC （HITACHI L-7420）. The genetic polymorphisms of CYP2E1 （Pst1 and Dra1）, and GST （T1 and M1） were determined by polymerase chain reaction （PCR） and restriction fragment length polymorphism （RFLP） from the peripheral lymphocytes. We found the average concentrations of DMF in air, DMF, NMF, and AMCC in urine were 7.59 ppm, 0.76, 9.36, and 15.29 mg/L, respectively. No any biomarkers in urine present associations with the CYP2E1 variants. Urinary AMCC, however, revealed a significant association with the variants of both GSTT1 and GSTM1 given adjusted by DMF concentrations in air. We suggested using urinary AMCC as a biomarker of DMF exposure should take into account of GST variants to avoid the erroneous exposure estimate.