Factors influencing the induction of sister chromatid exchanges in mammalian cells by 12-O-tetradecanoyl-phorbol-13-acetate.

The induction of sister chromatid exchanges (SCE) by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was measured in mouse 10T1/2 and 3T3 cells released from density; inhibition, and Chinese hamster CHO cells synchronized by mitotic selection. The induced frequency of SCE was similar in each cell type, but depended upon the concentration of TPA employed, its source, and the particular lot from the same source. Most SCE occurred in the first two rounds of cell replication after addition of TPA. The induction of SCE by TPA was markedly suppressed if the fetal calf serum in the incubation medium was not heat-inactivated. The addition of superoxide dismutase to medium with heat-inactivated serum also suppressed the induction of SCE. These results suggest that free radicals, particularly the superoxide anion, may be important intermediates in some of the biologic effects of TPA.