title: 32P Postlabelling analysis of urinary mutagens from smokers of black tobacco implicates 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) as a major DNA-damaging agent.
abstract: 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-phenylimidazo[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 postlabelling data which implicates PhIP as a mutagen in the urine of smokers of black tobacco.
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Peluso
authors.forename: M
authors.initials: M
authors.lastname: Castegnaro
authors.forename: C
authors.initials: C
authors.lastname: Malaveille
authors.forename: M
authors.initials: M
authors.lastname: Friesen
authors.forename: L
authors.initials: L
authors.lastname: Garren
authors.forename: A
authors.initials: A
authors.lastname: Hautefeuille
authors.forename: P
authors.initials: P
authors.lastname: Vineis
authors.forename: F
authors.initials: F
authors.lastname: Kadlubar
authors.forename: H
authors.initials: H
authors.lastname: Bartsch
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002855:Chromatography, Thin Layer / Q000379:methods; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D006801:Humans; D007093:Imidazoles / Q000378:metabolism / Q000633:toxicity* / Q000652:urine; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity; D009711:Nucleotides / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010947:Plants, Toxic; D012907:Smoking / Q000378:metabolism / Q000652:urine*; D014026:Nicotiana / Q000737:chemistry
chemical_list: D007093:Imidazoles; D009153:Mutagens; D009711:Nucleotides; D010761:Phosphorus Radioisotopes; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; D004247:DNA; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine