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

Hal B. Jenson, Jacques Baillargeon, Patty Heard, Mary Pat Moyer

Research output: Contribution to journalArticle

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)171-182
Number of pages12
JournalToxicology and Applied Pharmacology
Issue number2
StatePublished - Oct 15 1999
Externally publishedYes



  • 12-O-tetradecanoyl phorbol-13-acetate (TPA)
  • 4-(N-methyl-N-nitrosamine)-13-pyridinyl)-l-butanone (NNK)
  • Apoptosis
  • Epstein-Barr virus
  • Lymphocytes
  • N-butyrate
  • N-nitrosonornicotine (NNN)
  • Smokeless tobacco

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this