Abstract12‐O‐Tetradecanoyl‐phorbol‐13‐acetate (TPA) in conditions that produce enhancement of ultraviolet light (UV) and x‐irradiation Syrian hamster embryo cell (HEC) transformation did not cause further increase in the sister chromatid exchange (SCE) frequency induced by UV and x‐irradiation, two physical carcinogens that differ in their mode of DNA interaction and efficiency of SCE induction. Several factors which might influence SCE induction by TPA were studied on HEC and Chinese hamster V79‐4 cells. Heat‐inactivated serum was used because of the possibility that a serum component may interfere with TPA ability to cause SCE. TPA effect on SCE was determined at the first and second division post treatment on cells exposed to different 5‐bromodeoxyuridine (BrdUrd) concentrations. Independent of BrdUrd concentration (1‐10μg/ml medium) and the number of cell divisions post treatment, TPA (0.01‐2μg/ml medium) was ineffective in inducing SCE in exponentially and stationary HEC cultures cultivated in medium supplemented with heat‐inactivated serum. Also, TPA did not increase the SCE frequency in V79‐4 Chinese hamster cells cultured in heat‐inactivated or noninactivated serum. Although SCE induction, a cellular response to carcinogen‐induced DNA damage, may be important for the induction of transformation by environmental agents, the enhancement of transformation frequency caused by TPA occurs without further DNA alte