Mutagenesis vol. 5 no. 5 pp. 447-451, 1990
© 1990 UK Environmental Mutagen Society/Oxford University Press
research-article |
Cytotoxic and mutagenic effect of UV, ethylnitrosourea and (±)-7ß8,8
-dihydroxy-9
,10
-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene in diploid human T lymphocytes in culture: comparison with fibroblasts
Carcinogenesis Laboratory, Fee Hall, Department of Microbiology and Department of Biochemistry, Michigan State University East Lansing, MI 48824-1316, USA 1Present address: Department of Radiation Biology and Health, University of Occupational and Environmental Health (Japan) 1-1 Iseigaoka Yahatanishi-ku, Kitakyushu 807, Japan
The cytotoxic and mutagenic effects of a series of carcinogenic mutagens in human peripheral blood T cells exposed in culture were determined and compared with results obtained previously with diploid human skin fibroblasts. The mutagens studied were: ethylnitrosourea (ENU), (±)-7ß3,8
-dihydroxy-9
,10
-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and UV (254 nm) radiation. Resistance to 6-thioguanine (TG) served as the genetic marker. The T lymphocytes, cultured in the presence of 10% fetal bovine serum, T cell growth factor and lethally-irradiated B lymphoblastoid cells (allogeneic stimulators), exhibited population doubling times of 22 h for as long as tested, i.e. >40 days, and cloning efficiencies between 30 and 50%. The T cells were exposed to the mutagens in exponential growth, 3 days after being isolated and primed to begin blast formation, using doses that reduced cell survival to between 80 and 25% of the untreated control. The background frequency of TG-resistant cells in the 14 independent populations assayed ranged from 1.2x106 to 10.6x106, with an average of 5.1x106 ± 2.8 x106. Each agent induced a dose-dependent increase in TG-resistant cells, reaching 85x106 for UV, 260x106 for ENU and 70x106 for BPDE. When compared on the basis of fluence or applied concentration, T cells were 1.5-times more sensitive than fibroblasts to the cytotoxic effects of ENU, but equally as sensitive as fibroblasts to its mutagenic effects. They were 2.7-times more sensitive than fibroblasts to BPDE-induced cytotoxicity, but 2-times less sensitive to its mutagenicity. T lymphocytes and fibroblasts were about equal in sensitivity to the cytotoxic effect of UV, but T cells were 2-times less sensitive to the mutagenic effects of UV.