Influence of GSTM1 null and low repair XPC PAT+ on anti-B[a]PDE-DNA adduct in mononuclear white blood cells of subjects low exposed to PAHs through smoking and diet

The influence of low-activity NER genotypes ( XPC PAT−/ +, XPA- A23G, XPD Asp312Asn, XPD Lys751Gln) and GSTM1 ( active or null) was evaluated on anti-benzo[ a]pyrene diol epoxide-(B[ a]PDE)-DNA adduct formed in the lymphocyte plus monocyte fraction (LMF). The sample population consisted of 291 healthy subjects with low exposure to polycyclic aromatic hydrocarbons (PAHs) (B[ a]P) through their smoking ( n = 126 smokers) or dietary habits ( n = 165 non-smokers with high (≥52 times/year) consumption of charcoaled meat or pizza). The bulky anti-B[ a]PDE-DNA adduct levels were detected by HPLC/fluorescence analysis and genotypes by PCR. Anti-B[ a]PDE-DNA was present (≥0.5 adducts/10 8 nucleotides) in 163 (56%) subjects (median (range) 0.77 (0.125–32.0) adducts/10 8 nucleotides), with smokers showing a significantly higher adduct level than non-smokers with high consumption of PAH-rich meals ( P < 0.01). Our exposed-sample population with unfavourable XPC PAT+/− or +/+ and GSTM1 null genotypes has the significantly highest adduct level ( P < 0.01). Taking into account tobacco smoke and diet as sources of exposure to B[ a]P, low-activity XPC PAT+ shows a major role in smokers ( P < 0.05) and GSTM1 null in non-smokers with frequent consumption of PAH-rich meals ( P < 0.01). The modulation of anti-B[ a]PDE-DNA adduct in the LMF by GSTM1 null and low-activity XPC PAT+ polymorphisms may be considered as potential genetic susceptibility factors that can modify individual responses to low PAH (B[ a]P) genotoxic exposure, with the consequent risk of cancer in the general population.