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Micronuclei Related to Anti–B[a]PDE-DNA Adduct in Peripheral Blood Lymphocytes of Heavily Polycyclic Aromatic Hydrocarbon–Exposed Nonsmoking Coke-Oven Workers and Controls

¹ Occupational Health Section, Department of Environmental Medicine and Public Health, University of Padova, Via Giustiniani 2, Padova, Italy; ² Institute of Occupational Medicine and Environmental Health, Department of Genetic Toxicology, Koscielna 13, Sosnowiec, Poland; and ³ Environmental Carcinogenesis Unit, National Cancer Research Institute, L.go Rosanna Benzi, 10, Genoa, Italy

Requests for reprints: Sofia Pavanello, University of Padova, via Giustiniani 2, Padova, 35128 Italy. Phone: 390498216600; Fax: 390498212542. E-mail: sofia.pavanello{at}unipd.it

Micronuclei (MN) frequency associated to biologically effective dose of polycyclic aromatic hydrocarbons [PAH; anti-benzo[a]pyrene diolepoxide (B[a]PDE)-DNA] within the same subjects' peripheral blood lymphocytes (PBL) was evaluated. Study subjects were nonsmoking male Polish coke-oven workers (n = 49) and matched controls (n = 45) verified for PAH exposure by urinary 1-pyrenol. We found that coke-oven workers, heavily exposed to PAHs (80% workers exceeded the urinary 1-pyrenol biological exposure index value), presented significantly higher MN frequency in PBLs than controls (P < 0.01). Substantial difference was also found for adduct levels in PBLs (P < 0.01). Increase in MN levels was significantly related to anti–B[a]PDE-DNA formation, key adduct of the ultimate carcinogenic metabolite of B[a]P (n = 94; r = 0.47; P < 0.001). The dose-response relationship was improved when subjects with adduct levels above the 3rd tertile (4.35 adducts/10⁸ nucleotides) were excluded (n = 61; r = 0.69; P < 0.001). Saturation of adduct/MN formation at high levels may disturb the underlying relationship. Linear multiple regression analysis, without subjects of 3rd tertile adduct level (n = 61), revealed that adduct formation (t = 4.61; P < 0.001), but not 1-pyrenol, was the significant determinant in increasing MN. In conclusion, the increase in MN frequency is mainly related to the specific anti–B[a]PDE-DNA formation within PBLs of the same subject. Our results substantiate, with the use of an early indicator of biological effect as well, that workers are at higher cancer risk than controls.(Cancer Epidemiol Biomarkers Prev 2008;17(10):2795–9)