Genetic Polymorphism of CYP2E1, GSTT1/M1 and NQO1 on Biomarker of Urinary Spma Among Benzene-Exposed Workers

Abstract

P-268 Abstract: Benzene is a common organic solvent used in industry. One of the current biomarkers of benzene exposure is urinary S-phenylmercapturic acid (U-SPMA) at post-shift. Cytochrome P450 2E1 (CYP2E1) and glutathione-S-transferase (GST) are involved in the biotransformation of S-PMA. Thus, the genetic polymorphism of aforementioned enzymes could affect the biotransformation of exposed benzene and the health effects. The purpose of this study is to investigate the effects of various genetic polymorphisms on S-PMA kinetics. Seventy-four petrochemical workers directly exposed to benzene were environmentally monitored by breathing zone sampling coupled with gas chromatography analysis. Urine samples were collected at post-shift, during 8-hour complete work-shift and during 24-hr post-exposure since the end of the exposure. S-PMA in urine was analyzed by high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Blood samples were collected from each participant and were used to determine their genetic polymorphisms of CYP2E1, and GST by PCR (Polymerase Chain Reaction) and RFLP (Restriction fragment length polymorphism). We found: 1. Airborne benzene and urinary S-PMA measurements were shown as log-normally distributed and their geometric means were 6.52 ppb and 0.39 μg/g Cr., respectively, far below the current permissible exposure limit and biological exposure index; 2. Significant association between airborne benzene concentrations and U-SPMA at post-shift was found (r=0.39′P<0.01). 3. For those who were determined for their S-PMA throughout 8-hr complete work-shift and post-shift, significant association of airborne benzene concentrations with AUCS-PMA (area under curve) (r=0.62′P <0.05), but not with S-PMA at post-shift, was found; 4. AUCS-PMA at 24-hr post-shift were found significantly different between smokers and non-smokers (P<0.05); 5. The natural-transformed ratios of S-PMA to airborne benzene in those subjects with non-null GSTT1 type were significantly higher than those with null type. We concluded that 1. Because the AUC of S-PMA within 8-hr work-shift was better correlated with benzene exposure levels than S-PMA concentrations at post-shift, the biological monitoring of benzene exposure might consider using AUC to calibrate the total body burden while benzene exposure is low; 2. Cigarette smoking should be taken into consideration of biological monitoring of benzene exposure; 3. GSTT1 genetic polymorphism might affect the S-PMA levels and possibly due to insufficient sample size, this study was unable to determine the effect of the genetic polymorphism on S-PMA AUC.