CYTOTOXIC AND MUTAGENIC EFFECT OF UV, ETHYLNITROSOUREA AND (+/-)-7-BETA,8-ALPHA-DIHYDROXY-9-ALPHA,10-ALPHA-EPOXY-7,8,9,10-TETRAHYDRO-BENZO[A]PYRENE IN DIPLOID HUMAN LYMPHOCYTE-T IN CULTURE - COMPARISON WITH FIBROBLASTS

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), (±)-7β3,8α-dihydroxy-9α,10α-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 1.2×10-6 to 10.6×10-6, with an average of 5.1×10-6 ± 2.8 ×10-6. Each agent induced a dose-dependent increase in TG-resistant cells, reaching 85×10-6 for UV, 260×10-6 for ENU and 70×10-6 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. © 1990 Oxford University Press.