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32Postabelling analysis of urinary mutagens from smokers of black tobacco implicates 2-amino-1-methyl-6-phnylimidazo[4,5-b]pyridine (PhIP) as a major DNA-damaging agent
International Agency for Research on Cancer 150 Cours Albert Thomas, 69372 Lyon Cedex 08, France
1University of Turin Via Santena 7, 10126 Turin, Italy
2National Center for Toxiocological Research Jefferson, AR 72079, USA
3Present address: National Institute or Research on Cancer Viale Benedetto XV, 10, 16132 Genoa, Italy
4To whom reprint requests should be addressed
When mutagens extracted from the urine of two smokers of black tobacco were reacted with DNA in vitro in the presence of a metabolic activation system, several DNA adducts were detected by 32P-postlabelling analysis. Some of these adducts were also visible, but only faintly, on the autoradiogram for a non-smoker's urine. DNA adducts produced in vitro by 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or 2-amino-1-methyl-6-phenlimidazo[3,5-b]pyridine could not account for the adduct pattern produced by the urinary mutagens. However, three or four 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-related DNA adducts were present among the five or six adducts observed for smokers in the autoradiograms of urinary mutagen-adducted nucleotides. Mutagenicity testing combined with HPLC fractionation of urinary extracts also supported the patlabelling data which implicates PhIP as a mutagen in the urine of smokers of black tobacco.
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