Persistence of SCE-inducing lesions after G0 exposure of human lymphocytes to differing classes of DNA-damaging chemicals.
We conducted studies to determine whether cycling human lymphocytes are equally efficient in repairing sister chromatid exchange (SCE)-producing lesions induced by differing classes of DNA-damaging chemicals. Lymphocytes were pulse-treated during G0 with mitomycin C (MMC), N,N',N''-triethylenethiophosphoramide (ThioTEPA), ethylmethanesulfonate (EMS), or cis-diamminedichloroplatinum (cis-DDP). Bromodeoxyuridine (BrdUrd) was added to the 72 hr cultures at 0 hr or at 48 hr after phytohemmagglutinin stimulation. The concentrations of chemicals employed induced a greater than 2-fold increase in SCEs in second-division metaphases from lymphocytes cultured in the presence of BrdUrd for the entire 72 hr. The analysis of SCEs in uniformly harlequinized metaphases from G0-treated lymphocytes cultured in BrdUrd for the terminal 24 hr showed no increase above baseline after exposure to MMC, and intermediate increases above baseline after exposures to ThioTEPA and cis-DDP. However, after G0 treatment with EMS, the observed SCE frequency was consistent with that expected had all DNA lesions persisted and continued to give rise to SCEs during 3 cell cycles. These findings suggest that cycling human lymphocytes are not equally efficient in eliminating SCE-producing lesions after exposure to differing classes of DNA-damaging chemicals.
D000477:Alkylating Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D004260:DNA Repair; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D006801:Humans; D007399:Interphase; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure*; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D013852:Thiotepa / Q000494:pharmacology
D000477:Alkylating Agents; D008937:Mitomycins; D016685:Mitomycin; D013852:Thiotepa; D005020:Ethyl Methanesulfonate; D002945:Cisplatin