Effects of gene polymorphisms of CYP1A1, CYP1B1, EPHX1, NQO1, and NAT2 on urinary 1-nitropyrene metabolite concentrations

Abstract

Nitropyrene (1-NP) is a specific indicator of exposure to diesel exhaust and is partly metabolized to 1-aminopyrene (1-AP) and N-acetyl-1-aminopyrene (1-NAAP), which are excreted in urine. This study was conducted to evaluate the effects of gene polymorphisms of metabolic enzymes for 1-NP on the urinary concentrations of 1-AP and 1-NAAP. The study participants were 70 South Koreans who were occupationally or environmentally exposed to diesel exhaust. To evaluate 1-NP exposure levels, we sampled airborne particulate matters with a personal air sampler and measured urinary 1-AP and 1-NAAP concentrations. The genetic polymorphisms of the 1-NP metabolic enzymes (CYP1A1, CYP1B1, EPHX1, NQO1, and NAT2) were determined by direct sequencing. The mean 1-NP exposure level was 20.40 pg/m3, and the mean urinary concentrations of 1-AP and 1-NAAP were 0.074 nM and 0.213 nM, respectively. The correlation coefficient between the 1-NP exposure level and urinary 1-AP concentrations was 0.0138 and that between the 1-NP exposure level and urinary 1-NAAP concentrations was 0.1493, and neither correlation coefficient was statistically significant. The correlation coefficient between the 1-NP exposure level and urinary 1-AP concentrations showed statistically significant differences according to the CYP1A1 and CYP1B1 genotypes, and that between the 1-NP exposure level and urinary 1-NAAP concentrations was significantly different according to the CYP1A1, CYP1B1, and NAT2 genotypes. The urinary concentration of 1-NAAP is a better biomarker for exposure to 1-NP or DEPs because the former is higher, easier to measure, and more strongly correlated with 1-NP exposure levels than that of 1-AP. The relationship between 1-NP exposure and urinary 1-AP or 1-NAAP concentration depends on the single nucleotide polymorphism types of CYP1A1, CYP1B1, NQO1, and NAT2.