title: Nicotine, cotinine, and b-nicotyrine inhibit NNK-induced DNA-strand  break in the hepatic cell line HepaRG.
abstract: Recent in vitro work using purified enzymes demonstrated that nicotine and/or a nicotine metabolite could inhibit CYPs (CYP2A6, 2A13, 2E1) involved in the metabolism of the genotoxic tobacco nitrosamine NNK. This observation raises the possibility of nicotine interaction with the mechanism of NNK bioactivation. Therefore, we hypothesized that nicotine or a nicotine metabolite such as cotinine might contribute to the inhibition of NNK-induced DNA strand breaks by interfering with CYP enzymes. The effect of nicotine and cotinine on DNA strand breaks was evaluated using the COMET assay in CYP competent HepaRG cells incubated with bioactive CYP-dependent NNK and CYP-independent NNKOAc (4-(acetoxymethylnitrosoamino)-1-(3-pyridyl)-1-butanone). We report a dose-dependent reduction in DNA damage in hepatic-derived cell lines in the presence of nicotine and cotinine. Those results are discussed in the context of the in vitro model selected.
authors.lastname: Ordonez
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Sierra
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Camacho
authors.forename: Andrew
authors.initials: A
authors.lastname: Baxter
authors.forename: Anisha
authors.initials: A
authors.lastname: Banerjee
authors.forename: David
authors.initials: D
authors.lastname: Waters
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Minet
mesh_terms: D045744:Cell Line, Tumor; D002478:Cells, Cultured; D020552:Comet Assay; D003367:Cotinine / Q000494:pharmacology*; D065637:Cytochrome P-450 CYP2A6 / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008099:Liver / Q000378:metabolism; D009602:Nitrosamines / Q000633:toxicity*; D011725:Pyridines / Q000494:pharmacology* / Q000633:toxicity*
chemical_list: D009602:Nitrosamines; D011725:Pyridines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6; D003367:Cotinine