METABOLIC POLYMORPHISMS AND URINARY BIOMARKERS IN SUBJECTS WITH LOW BENZENE EXPOSURE

Abstract

The effect of some common metabolic polymorphisms on the rate of trans,trans -muconic acid (TMA) and S -phenylmercapturic acid (SPMA) excretion was investigated in 169 policemen exposed to low benzene levels (<10 µg/m 3 ) during the work shift. End-shift urinary concentrations of TMA and SPMA, normalized to unmetabolized blood benzene concentration, were used as indicators of individual metabolic capacity. CYP2E1, NQO1, GSTM1, and GSTT1 polymorphisms were analyzed in all subjects by polymerase chain reaction (PCR)-restriction fragment length (RFL). The results obtained show significantly elevated levels of TMA and SPMA in urine of smokers compared to nonsmokers, whereas no correlation with environmental benzene was observed. TMA/blood benzene ratio was partially modulated by glutathione S -transferase (GST) genotypes, with significantly higher values in null individuals (GSTM1 and GSTT1 combined). However, a greater fraction of total variance of TMA/blood benzene in the study population was explained by other independent variables, that is, season of sampling, smoking habits, and gender. Variance in SPMA/blood benzene ratio was only associated with smoking and occupation, whereas no significant role was observed for the metabolic polymorphisms considered. These results suggest that in a population exposed to very low benzene concentrations, urinary TMA and SPMA levels are affected to a limited extent by metabolic polymorphisms, whereas other factors, such as gender, lifestyle, or other confounders, may account for a larger fraction of the interindividual variability of these biomarkers.