title: Acute in vivo treatment with 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone does not alter base excision repair activities in murine lung and liver.
abstract: 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary carcinogen found in unburned tobacco and tobacco smoke, and is believed to play an important role in human tobacco-induced cancers. In previous studies, NNK has been reported to induce oxidative DNA damage, and to alter DNA repair processes, effects that could contribute to pulmonary tumorigenesis in rodent models. The goal of this study was to determine the effects of NNK on levels of 8-hydroxydeoxyguanosine (8-OHdG), a biomarker of DNA oxidation, and activity of base excision repair (BER), which repairs oxidative DNA damage. Female A/J mice were treated with a tumorigenic dose of NNK (10μmol) i.p. At 1, 2 and 24h post treatment, there were no statistically significant differences in lung or liver 8-OHdG levels between control and NNK-treated mice (P>0.05). Furthermore, NNK did not alter lung or liver BER activity compared to control at any time point (P>0.05). In summary, acute treatment with a tumorigenic dose of NNK did not stimulate oxidative DNA damage or significantly alter BER activity, and these effects may not be major mechanisms of action of NNK in mouse models.
authors.affiliation: Pharmacology and Toxicology Graduate Program, Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Gupta
authors.forename: R Mason
authors.initials: RM
authors.lastname: Curtis
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Mulder
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Massey
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008168:Lung / Q000187:drug effects*; D051379:Mice; D023421:Models, Animal; D009602:Nitrosamines / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine
keywords: 2′-dG; 2′-deoxyguanosine; 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone; 4-methylnitrosamino-1-(3-pyridyl)-1-butanone; 8-Hydroxydeoxyguanosine; 8-OHdG; 8-hydroxydeoxyguanosine; 8-oxoguanine glycosylase 1; BER; Base excision repair; DFO; DNA repair; HPLC-ECD; MGMT; NER; NNK; O(6)-methylguanine methyltransferase; OGG1; Oxidative DNA damage; base excision repair; deferoxamine mesylate; high-performance liquid chromatography with electrochemical detection; nucleotide excision repair