Induction of sister chromatid exchanges by tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in human and hamster cells.
4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a nicotine derived N-nitrosamine, is a carcinogen that induces tumors in mice, rats and hamsters. To assess the ability of NNK to interact with the cellular DNA as an essential step in carcinogenesis, the induction of sister chromatid exchange (SCE) was examined in cultured normal human lymphocytes (HL) and Chinese hamster V79 cells. SCE formation is a sensitive indicator of carcinogen-DNA interaction that correlates with the induction of mutation and neoplastic cell transformation. HL and V79 cells were treated for 2 h with 20, 50, 100 and 200 micrograms/ml of NNK with and without application of metabolic activation S-9 mixture, and subsequently incubated for two rounds of replication in the presence of 5-bromodeoxyuridine required for SCE visualization. In V79 cells NNK produced a dose-dependent increase in SCE only with metabolic activation. In HL NNK induced a small but statistically significant increase in SCE with or without metabolic activation. These data provide the first evidence that NNK and/or its metabolic derivatives are able to induce DNA damage leading to SCE formation both in hamster and human cells. The differences in response between the two cell types suggests the existence of a difference in susceptibility associated with NNK metabolism and its interaction with cellular DNA.
Zimonjic
D
D
Division of Cancer Etiology, National Cancer Institute, Bethesda, MD 20892.
Popescu
N C
NC
DiPaolo
J A
JA
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes; D009602:Nitrosamines / Q000494:pharmacology*; D012854:Sister Chromatid Exchange
D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone