title: Morphologic and growth effects of tobacco-associated chemical carcinogens and smokeless tobacco extracts on human oral epithelial cells in culture.
abstract: Epidemiologic studies show an increase in the use of smokeless tobacco but few in vitro studies have directly assessed the potential for smokeless tobacco-induced oral carcinogenesis. Oral keratinocytes were grown to 90% confluence from explants of human labial and gingival mucosa at 34 degrees C, 5% CO2 in defined media. Epithelial monolayers were subsequently subcultured and then treated for 1 hour with aqueous extracts of moist or leaf smokeless tobacco, or with 0.25 to 1.0 ng/ml of three common smokeless tobacco carcinogens: 4-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-1-butanone; N-nitrosonornicotine; and benzo(a)pyrene. Even though the controls and most treatment groups terminally differentiated, cells exposed to 4-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-1-butanone, N-nitrosonornicotine, and moist and dry extract continued to divide, maintained a differentiated phenotype for 8 1/2 to 10 weeks in culture, and displayed focal growth and morphologic changes suggestive of early stages in cell transformation.
authors: Department of Pathology, University of Texas Health Science Center, San Antonio.
authors: V A
authors: VA
authors: Murrah
authors: E P
authors: EP
authors: Gilchrist
authors: M P
authors: MP
authors: Moyer
mesh_terms: D000704:Analysis of Variance; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D009061:Mouth Mucosa / Q000187:drug effects*; D009602:Nitrosamines / Q000633:toxicity; D010947:Plants, Toxic; D014030:Tobacco, Smokeless / Q000633:toxicity*
chemical_list: D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C008655:N'-nitrosonornicotine