Caffeine enhancement of chemical carcinogen-induced transformation of cultured Syrian hamster cells.

depends upon: (a) concentration of caffeine; (fc) time of addition of caffeine; (c) length of exposure; and (d) carcinogen used. The addition of caffeine to cells treated 1 hr previously with carcinogen resulted in the potentiation of toxicity. Toxicity increased with caffeine concentration and length of exposure to carcinogen-containing medium. With 50 ¿ig caffeine per ml medium for 2 days cloning efficiency, the number of cells forming colonies relative to the number of cells plated was reduced approximately 20 to 30%. When 50 or 100 /ug caffeine per ml medium were added 1 hr after the carcinogen and allowed to remain for 48 hr, the absolute number of transformations increased and an enhancement ratio of 3 to 6 resulted (the number of transformations obtained by thà ̈double treatment divided by that obtained by carcinogen only). Caffeine added 1 hr prior to the carcinogen did not increase toxicity or alter the transformation fre quency. When 0.5 to 200 ¿/gcaffeine per ml medium was added 1 hr post-AcAAF, cloning efficiency decreased and average number of transformations increased with caffeine concentration. The addition of a constant amount of caffeine (50 Mg/ml) f°r48 hr at different intervals after carcinogen resulted in maximum enhancement (10 to 17) when caffeine was added at 4 hr. With AcAAF, the addition of caffeine at later intervals such as 24 and 48 hr caused no enhancement, whereas with ./V-methylW'-nitroW-nitrosoguanidine the en