A possible involvement of DNA topoisomerase I in "caffeine effect" after ultraviolet irradiation

Caffeine has been known to enhance lethal and chromosome damaging effects of chemical and physical mutagens. In spite of numerous investigations, the mechanism is not fully elucidated. In this paper, we describe that 1) post-treatment with camptothecin (CPT), a specific inhibitor of DNA topoisomerase (topo) I, enhances SCE-induction by ultraviolet light (UV), as post-UV caffeine treatment does, 2) the lethal effect of UV is also enhanced but to a lesser degree than by post-UV caffeine treatment, and 3) caffeine, like CPT, inhibits calf thymus topo I activity, as determined by relaxation of pBR322 supercoiled DNA. These results suggest that the mechanism(s) of lethal and SCE enhancement involves the ability of caffeine to inhibit topo I.