Association between GST genetic polymorphism and dose-related production of urinary benzene metabolite markers, trans, trans-muconic acid and S-phenylmercapturic acid.

The urinary benzene metabolites, trans, trans-muconic acid (ttMA) and S-phenylmercapturic acid (SPMA), are widely used as benzene exposure biomarkers. The influence of the glutathione S-transferase (GST) genetic polymorphism on the excretion levels of urinary ttMA and/or SPMA has been investigated. The association between dose-related production of urinary benzene metabolites and benzene exposure level was also reported. However, the association between the dose-related productions of urinary benzene metabolites and GST genetic polymorphism was not described in the literature. The purpose of this study was to investigate the association between the GST genetic polymorphism and dose-related production of the two widely used biomarkers, urinary ttMA and SPMA. Seventy male workers in a chemical factory were measured for their benzene exposure levels and provided blood and urine specimens at the end of work-shift. The atmospheric benzene exposure levels of these workers were determined by passive samplers with gas chromatograph mass spectrometer. The urinary ttMA and SPMA levels were quantitated by an online dual-loop cleanup device with an electrospray ionization tandem mass spectrometer. The analyses of GST genotypes, including M(1), T(1), and P(1), were done using PCR. Mean (+/- SD) of benzene exposure levels in participants was 7.2 +/- 15 ppm. The ttMA and SPMA levels in the high benzene exposure group (> or =1 ppm) were higher than those in the low benzene exposure group (<1 ppm; P < 0.001). Among the GST genotypes investigated in this study, the results showed that only the GSTT1 genotype was related to the level and dose-related production of SPMA. Using SPMA for evaluating benzene exposure, the results suggest that the GSTT1 genetic polymorphism, especially in a comparison study between two populations with different GSTT1 genotype frequencies, should be considered. Additionally, the biological exposure index value of SPMA should be set based on the levels of subjects with GSTT1-deficient genotypes for protection of all subjects.