Susceptibility and exposure biomarkers in people exposed to PAHs from diesel exhaust

Xenobiotic metabolizing enzymes, especially CYP1A1 and GSTM1, are involved in the activation and conjugation of PAHs and are controlled by polymorphic genes. PAHs released from diesel emissions in many cities of the world, especially in developing countries, contribute significantly to the toxic effects of airborne inhalable particles. We have evaluated the gene-environment interaction in Santiago of Chile, studying the contribution of CYP1A1 and GSTM1 polymorphisms on 1-OH-P urinary levels used as the PAHs exposure biomarker. The study was performed on 59 diesel exposed (38 diesel revision workers and 21 subjects working in an urban area as established street vendors) and 44 non-exposed subjects living in a rural area. The 1-OH-P urinary levels of the urban (P=0.043) and rural (P=0.040) populations showed, without considering the genotypes, significant differences between smokers and non-smokers, but no significant differences were found between smokers and non-smokers among the diesel plant workers (P=0.33). Non-smoking subjects of the diesel plants and the urban area showed similar 1-OHP levels (P=0.466) which were significantly higher than those of the subjects living in the rural area (P<0.05). When 1-OH-P levels were related with genotypes, an association was observed for the CYP1A1*2A genotype, so that the diesel-exposed workers carrying the CYP1A1*2A allele showed significantly higher 1-OH-P levels than the subjects from the rural area with the same genotype (P=0.008). On the other hand, there was no significant correlation between urinary 1-OH-P levels and GSTM1 null genotype, although higher levels of the urinary metabolite were found in individuals carrying the combined CYP1A1*2A and GSTM1 null genotype (P=0.055). These results may suggest an association between levels of the exposure biomarker 1-OH-P and presence of the CYP1A1*2A genotype, a potential genetic susceptibility biomarker which might be useful in identifying individuals at higher risk among people exposed to high PAH levels in diesel exhaust.