32P-postlabelling analysis of DNA-adducts formed by 4-(N-carbethoxy-N-nitrosamino)-(3-pyridyl)-1-butanone and 4-oxo-4-(3-pyridyl)- butanal.
The tobacco-specific nitrosamine, 4-(N-nitrosomethylamino)-1-(3-pyridyl)- 1-butanone (NNK) can be activated to DNA-binding species by two pathways: methylene hydroxylation leads to an equimolar formation of methyldiazohydroxide and 4-oxo-4-(3-pyridyl)-butanal followed by DNA methylation, while methyl hydroxylation leads to DNA pyridyloxobutylation via the 4-(3-pyridyl)-4-oxobutyldiazohydroxide (Hecht et al., 1988; Spratt et al., 1989). We report here that the ketoaldehyde, 4-oxo-4-(3-pyridyl)-butanal, as well as 4-(N-carbethoxy-N-nitrosamino)-1-(3- pyridyl)-1-butanone (NNC), a model compound for pyridyloxobutylation, form DNA adducts in vitro, as detected by 32P-postlabelling assays. The two major adduct spots of both compounds were chromatographically indistinguishable, suggesting structurally similar DNA adducts.
Schmeiser
H H
HH
Department of Molecular Toxicology, German Cancer Research Centre, Heidelberg.
Castonguay
A
A
Wiessler
M
M
D000818:Animals; D001345:Autoradiography; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D002417:Cattle; D002855:Chromatography, Thin Layer; D004247:DNA / Q000032:analysis* / Q000737:chemistry / Q000187:drug effects*; D004249:DNA Damage; D006900:Hydroxylation; D066298:In Vitro Techniques; D009602:Nitrosamines / Q000378:metabolism / Q000633:toxicity*; D010761:Phosphorus Radioisotopes; D011725:Pyridines / Q000378:metabolism / Q000633:toxicity*
D002273:Carcinogens; D009602:Nitrosamines; D010761:Phosphorus Radioisotopes; D011725:Pyridines; C048585:4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone; C062145:4-oxo-4-(3-pyridinebutanal); D004247:DNA