Caffeine induces uncoordinated expression of cell cycle functions after ultraviolet irradiation. Accelerated cycle transit, sister chromatid exchanges and premature chromosome condensation in a transformed Indian muntjac cell line.

Abstract

Caffeine enhances the lethal effect of DNA-damaging agents. It also affects the timing of events in the cell cycle; the enhanced cytotoxicity may be partly due to caffeine's ability to overcome the protective damage-induced delay in S or G2 phase. When the effects of caffeine are compared in a normal Indian muntjac cell line and a simian virus 40 (SV40)-transformed, ultraviolet light (u.v.)-sensitive line in which u.v. induces many sister chromatid exchanges, different cell cycle sensitivities are seen. In the SV40-transformed line, caffeine over-rides the delay in DNA synthesis imposed by DNA damage; it initiates late cycle events after u.v. irradiation, and in some cases it induces S-phase premature chromosome condensation, apparently by inducing mitotic factors in cells where the chromatin is still replicating. Caffeine has been reported to induce similar premature chromosome condensation in cells arrested with DNA polymerase inhibitors; this is the first recognition that such events occur in response to caffeine treatment after DNA damage. Some apparent paradoxes of caffeine's action on irradiated cells can be thus explained. In the normal line, caffeine neither affects progression through the cycle nor induces premature chromosome condensation after irradiation. In both lines, caffeine increases killing and sister chromatid exchanges after u.v. irradiation; but these effects are more pronounced when exerted through the cell cycle-related mechanism.