The effects of benzo(a)pyrene, nicotine, and tobacco-specific N-nitrosamines on the generation of human lymphokine-activated killer cells.
The effects of four major components of snuff (fine-cut smokeless tobacco) on the development of lymphokine-activated killer cells (LAK) were measured in vitro. Of the components tested: nicotine, N'-nitrosonornicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo(a)pyrene (BaP), only BaP suppressed LAK cytotoxicity against tumour targets and LAK DNA synthesis during 3- and 7-day incubations. BaP concentrations of 0.1-1.0 micrograms/ml suppressed lymphocyte proliferation only; there was no effect on tumour cell proliferation at these concentrations. BaP had no effect on tumour target killing when incubated during 4 h natural killer (NK) or LAK cytotoxicity assays. There was no effect on LAK binding of tumour targets after 3 days culture with BaP concentration of 0.1-1.0 micrograms/ml. These data confirm that a water-soluble extract of snuff has anti-cytolytic and anti-proliferative effects on peripheral blood lymphocytes. As NK and LAK cells are important in preventing tumourigenesis and metastasis, suppression of these cells may favour neoplastic growth associated with snuff-dipping.
Lindemann
R A
RA
Section of Oral Diagnosis, Oral Medicine and Oral Pathology, UCLA School of Dentistry.
Park
N H
NH
D001580:Benzopyrenes / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D009602:Nitrosamines / Q000494:pharmacology*; D010947:Plants, Toxic; D014030:Tobacco, Smokeless; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001580:Benzopyrenes; D009602:Nitrosamines; D009538:Nicotine; D004247:DNA