Enhancement of 131I-mediated cytotoxicity by caffeine

In cell culture, caffeine has been shown to enhance the lethality of DNA-damaging agents including ultraviolet rays, X-irradiation, and alkylating agents. We have previously reported a Phase I clinical trial demonstrating the feasibility of intraperitoneal radioimmunotherapy in patients with refractory ovarian cancer using 131I-labeled monoclonal antibody OC125. We are now exploring the possibility of using caffeine to enhance the toxicity of 131I-irradiation in target cells. As an in vitro model we tested this hypothesis using Chinese hamster ovary (CHO) cells exposed to 131I-labeled human serum albumin at various doses (4 to 70 microCi/ml) for 24 hr followed by 24 hr of incubation with caffeine. Cytotoxicity was measured by clonogenic survival and a nuclear fragmentation assay. The results show that caffeine, at a concentration of 7.7 mM, significantly enhances the cytotoxicity of 131I-irradiation.