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.
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.
Peluso
M
M
International Agency for Research on Cancer, Lyon, France.
Castegnaro
M
M
Malaveille
C
C
Friesen
M
M
Garren
L
L
Hautefeuille
A
A
Vineis
P
P
Kadlubar
F
F
Bartsch
H
H
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
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