Cytotoxic and mutagenic effect of UV, ethylnitrosourea and (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo [a]pyrene in diploid human T lymphocytes 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), (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-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. greater than 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 x 10(-6) to 10.6 x 10(-6), with an average of 5.1 x 10(-6) +/- 2.8 x 10(-6). Each agent induced a dose-dependent increase in TG-resistant cells, reaching 85 x 10(-6) for UV, 260 x 10(-6) for ENU and 70 x 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Norimura
T
T
Department of Microbiology, Michigan State University, East Lansing 48824-1316.
Maher
V M
VM
McCormick
J J
JJ
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000328:Adult; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004351:Drug Resistance; D005038:Ethylnitrosourea / Q000633:toxicity*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D009152:Mutagenicity Tests; D009154:Mutation; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects; D013866:Thioguanine / Q000494:pharmacology; D014466:Ultraviolet Rays
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D013866:Thioguanine; D005038:Ethylnitrosourea