title: Effects of smokeless tobacco and tumor promoters on cell population growth and apoptosis of B lymphocytes infected with epstein-barr virus types 1 and 2.
abstract: The effects of smokeless tobacco purified products 4-(N-methyl-N-nitrosamine)-1-3-pyridinyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), smokeless tobacco extracts (dry snuff, moist snuff, and loose leaf), and the tumor promoters 12-O-tetradecanoyl phorbol-13-acetate (TPA) and n-butyrate on cell population growth, cell death, and apoptosis were studied in B lymphocyte cell lines harboring Epstein-Barr virus (EBV) type 1 (Raji and X50-7) or type 2 (HR-1K and AG876) and in an EBV-uninfected control lymphocyte cell line (Ramos). Spontaneous apoptosis was present in all EBV-infected cell lines, but at varying levels. Spontaneous and induced apoptosis were generally greater by Student-Newman-Keuls tests in cells harboring EBV type 2 compared to EBV type 1. The greatest effects on cell population growth, cell death, and apoptosis on cells harboring lytic EBV type 1 (X50-7) was with each of the three smokeless tobacco extracts. The greatest effects on cells harboring EBV type 2 was with TPA and n-butyrate. There were no effects of smokeless tobacco extracts on the Raji cell line that harbors EBV type 1 incapable of lytic replication. Smokeless tobacco purified products, NNN and NNK, had no discernible effects. At the concentrations used in these experiments, there appears to be an EBV type-specific response to chemical induction, with greater susceptibility of lytic EBV type 1 to smokeless tobacco extracts and lytic EBV type 2 to TPA and n-butyrate. This EBV type-specific susceptibility to the effects of smokeless tobacco extracts is another phenotypic difference between EBV types. The use of smokeless tobacco products may affect B lymphocytes infected with replication-capable EBV in the oropharynx. The absence of significant effects with NNK and NNN suggests that these properties reside with other compounds present in tobacco extracts.
authors.affiliation: Department of Pediatrics, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78284, USA. jenson@uthscsa.edu
authors.forename: H B
authors.initials: HB
authors.lastname: Jenson
authors.forename: J
authors.initials: J
authors.lastname: Baillargeon
authors.forename: P
authors.initials: P
authors.lastname: Heard
authors.forename: M P
authors.initials: MP
authors.lastname: Moyer
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology / Q000821:virology*; D002087:Butyrates / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D009602:Nitrosamines / Q000633:toxicity; D010947:Plants, Toxic; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D013997:Time Factors; D014030:Tobacco, Smokeless / Q000633:toxicity*; D014407:Tumor Cells, Cultured
chemical_list: D002087:Butyrates; D002273:Carcinogens; D009602:Nitrosamines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D013755:Tetradecanoylphorbol Acetate