Persistence of SCE-Inducing Lesions after GO Exposure of Human Lymphocytes to Differing Classes of DNA-Damaging Chemicals
We conducted studies to determine whether cycling human lympho cytes are equally efficient in repairing sister chromatid exchange (SCE)-producing lesions induced by differing classes of DNA-damaging chemicals. Lymphocytes were pulse-treated during GO with mitomycin C (MMC), N,N′,N″-triethylenethiophosphoramide (ThioTEPA), ethyl-methanesulfonate (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 GO-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 GO 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.
KeywordsHuman Lymphocyte Sister Chromatid Exchange Sister Chromatid Exchange Frequency Entire Culture Period Bifunctional Alkylating Agent
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