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 (>or=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 (>or=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.
Pavanello
Sofia
S
Occupational Health Section, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, 35128 Padova, Italy. sofia.pavanello@unipd.it
Pulliero
Alessandra
A
Clonfero
Erminio
E
D000217:Acyltransferases / Q000235:genetics*; D000328:Adult; D018736:DNA Adducts; D004268:DNA-Binding Proteins / Q000235:genetics*; D004032:Diet / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D000071518:Liver X Receptors; D008214:Lymphocytes / Q000000981:diagnostic imaging; D008297:Male; D008875:Middle Aged; D057093:Orphan Nuclear Receptors; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011110:Polymorphism, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*; D014463:Ultrasonography
D000217:Acyltransferases; D018736:DNA Adducts; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011084:Polycyclic Aromatic Hydrocarbons; D018160:Receptors, Cytoplasmic and Nuclear; C086984:XPC protein, human; C105599:HHAT protein, human