The influence of CYP1A1 and GSTM1 polymorphism on the concentration of urinary 1-hydroxypyrene in cPAHs exposed Iranian anode plant workers

摘要

Polycyclic aromatic hydrocarbons (PAHs) are a group of environmental pollutants in the occupational settings which are associated with an increased risk of cancer. CYP and GST enzymes have an important role in metabolism of PAHs. Genetic polymorphisms of these enzymes may affect their capacity for oxidation and detoxification of PAHs which will result in variation in PAHs metabolites. The aim of this study was to evaluate the association of urinary 1-hydroxypyrene levels with genetic polymorphisms of CYP1A1 and GSTM1 polymorphism in the Iranian anode plant workers. class="Para">The study population consisted of 42 workers working in carbon anode plant in an aluminum production industry and matched control group consisted of 43 office workers. Personal air sampling was performed to assess workers atmospheric exposure to carcinogenic PAHs. Blood samples were taken for DNA extraction and determination of GSTM1 and CYP1A1 polymorphism. Urine samples were taken immediately after the end of the working shift on the last working day for analysis of urinary 1-hydroxypyrene using High Performance Liquid Chromatography (HPLC). Statistical analysis was performed using SPSS ver. 16 software. class="Para">The mean concentration of occupational exposure to cPAHs in the exposed group was 11.42 μg/m3 ranging from 3.6 to 31.5 μg/m3. Mean level of urinary 1-hydroxypyrene in the exposed and control groups was 6.32±4.9 μmole/mole creatinine and 0.54±.48 μmole/mole creatinine respectively. According to the statistical analysis we found no influence of CYP1A1 MspI polymorphism on the urinary 1-hydroxypyrene levels of exposed and control subjects before and after stratification according to smoking habit. Our results also showed that, GSTM1 null genotype is associated with significantly higher levels of urinary 1-hydroxypyrene before stratification according to smoking habit in the exposed subjects (P=0.003) and after stratification the association remained statistically significant only in the non smoker subjects (P= 0.003). class="Para">Association of GSTM1 null genotype with higher levels of urinary 1-hydroxypyrene shows higher susceptibility of these genotype carriers to genotoxic effects of PAHs and employment of GSTM1 null carriers in the occupational settings with high levels of PAHs pollution should be reconsidered. Regarding the CYP1A1 polymorphism, it seems more studies, especially with large sample sizes, are necessary for achieving conclusive results.