Determinants of anti-benzo[a]pyrene diol epoxide-DNA adduct formation in lymphomonocytes of the general population.
We evaluated determinants of anti-benzo[a]pyrenediolepoxide-(B[a]PDE)-DNA adduct formation (adduct induced by the ultimate carcinogenic metabolite of B[a]P) in lymphomonocytes of subjects environmentally exposed to low doses of polycyclic aromatic hydrocarbons (PAHs) (B[a]P). Our study population consisted of 585 Caucasian subjects, all municipal workers living in North-East Italy and recruited during their periodic check-ups after informed consent. PAH (B[a]P) exposure was assessed by questionnaire. Anti-B[a]PDE-DNA levels were measured by HPLC fluorescence analysis. We found that cigarette smoking (smokers (22%) versus non-smokers, p<0.0001), dietary intake of PAH-rich meals (> or =52 (38%) versus <52 times/year, p<0.0001), and outdoor exposure (> or =4 (19%) versus <4h/day; p=0.0115) significantly influenced adduct levels. Indoor exposure significantly increased the frequency of positive subjects (> or =0.5 adducts/10(8) nucleotides; chi(2) for linear trend, p=0.051). In linear multiple regression analysis the major determinants of increased DNA adduct levels (ln values) were smoking (t=6.362, p<0.0001) and diet (t=4.035, p<0.0001). In this statistical analysis, indoor and outdoor exposure like other factors of PAH exposure had no influence. In non-smokers, the influence of diet (p<0.0001) and high indoor exposure (p=0.016) on anti-B[a]PDE-DNA adduct formation became more evident, but not that of outdoor exposure, as was confirmed by linear multiple regression analysis (diet, t=3.997, p<0.0001 and high indoor exposure, t=2.522, p=0.012). This study indicates that anti-B[a]PDE-DNA adducts can be detected in the general population and are modulated by PAH (B[a]P) exposure not only with smoking - information already known from studies with limited number of subjects - but also with dietary habits and high indoor exposure. In non-smokers, these two factors are the principal determinants of DNA adduct formation. The information provided here seems to be important, since DNA adduct formation in surrogate tissue is an index of genotoxic exposure also in target organs (e.g., lung) and their increase may also be predictive of higher risk for PAH-related cancers.
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
Saia
Bruno Onofrio
BO
Clonfero
Erminio
E
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis* / Q000737:chemistry; D000328:Adult; D000368:Aged; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D018736:DNA Adducts / Q000032:analysis* / Q000097:blood / Q000737:chemistry; D004032:Diet; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D004785:Environmental Pollutants / Q000506:poisoning; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000506:poisoning; D012044:Regression Analysis; D012307:Risk Factors; D012907:Smoking; D011795:Surveys and Questionnaires; D014028:Tobacco Smoke Pollution / Q000032:analysis
D018736:DNA Adducts; D004785:Environmental Pollutants; D011084:Polycyclic Aromatic Hydrocarbons; D014028:Tobacco Smoke Pollution; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide