Effects of smokeless tobacco and tumor promoters on cell population growthand apoptosis of B lymphocytes infected with Epstein-Barr virus types 1 and 2

The effects of smokeless tobacco purified products 4-(N-methyl-N-nitrosamin e)-1-3-pyridinyl)-1-butanone (NNK) and N-nitrosonornicotine (NNN), smokeles s tobacco extracts (dry snuff, moist snuff, and loose leaf), and the tumor promoters 12-O-tetradecanoyl phorbol-13-acetate (TPA) and n-butyrate on cel l 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 t ype 2 (HR-1K and AG876) and in an EBV-uninfected control lymphocyte cell li ne (Ramos), Spontaneous apoptosis was present in all EBV-infected cell line s, but at varying levels. Spontaneous and induced apoptosis were generally greater by Student-Newman-Keuls tests in cells harboring EBV type 2 compare d 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 o f the three smokeless tobacco extracts. The greatest effects on cells harbo ring EBV type 2 was with TPA and n-butyrate. There were no effects of smoke less tobacco extracts on the Raji cell line that harbors EBV type 1 incapab le 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 extrac ts and lytic EBV type 2 to TPA and n-butyrate. This EBV type-specific susce ptibility to the effects of smokeless tobacco extracts is another phenotypi c difference between EBV types. The use of smokeless tobacco products may a ffect B lymphocytes infected with replication-capable EBV in the oropharynx . The absence of significant effects with NNK and NNN suggests that these p roperties reside with other compounds present in tobacco extracts. (C) 1999 Academic Press.