Chromosome aberrations and DNA damage in a human gingival keratinocyte cell line induced by tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridy1)-1-butanone (NNK)

• Published in: Japanese Journal of Oral and Maxillofacial Surgery Vol. 43; no. 11; pp. 814 - 824
• Main Authors: MAEZAWA, Satoshi, UCHIDA, Minoru, TSUTSUI, Takeki
• Format: Journal Article
• Language: English
• Published: Japanese Society of Oral and Maxillofacial Surgeons 1997
• Subjects: 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); chromosome aberrations; cytotoxicity; unscheduled DNA synthesis (UDS)
• ISSN: 0021-5163; 2186-1579
• DOI: 10.5794/jjoms.43.814

The ability of tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) to induce chromosome aberrations and DNA damage was examined in an immortal cell line (NDUSD-1 cells) of human keratinocytes from gingival tissues. Treatment of NDUSD-1 cells with NNK at 1-10 mM for 3-10 days reduced cell survival in a dose-and treatment-time-dependent manner. Survival of cells treated with NNK (1-10 mM) for 7 days was similar to that of cells treated with NNK (1-10 mM) for 2 hours in the presence of exogenous metabolic activation with rat liver post-mitochondrial supernatant. No significant increases in the frequency of chromosome aberrations were observed in NDUSD-1 cells treated with NNK (1-10 mM) for 6 hours, but significant levels of chromosome aberrations were found in cells treated with NNK (3-10 mM) for 2 hours with exogenous metabolic activation. DNA damage as detected by unscheduled DNA synthesis (UDS) was not induced in cells exposed to NNK (0.1-10 mM) for 2 hours, but was induced in cells exposed to the same concentrations of NNK for 24 hours. Induction of UDS by NNK was also observed in cells treated with NNK (1-10 mM) for 2-6 hours in the presence of exogenous metabolic activation. These results suggest that conversion of NNK to active metabolites is required for the induction of cytotoxicity and genotoxicity of NNK in NDUSD-1 cells, and that NDUSD-1 cells retain a weak capability to metabolize NNK