ENHANCEMENT OF I-131 MEDIATED CYTOTOXICITY BY CAFFEINE

In cell culture, caffeine has been shown to enhance the lethality of D NA-damaging agents including ultraviolet rays, X-irradiation, and alky lating agents, We have previously reported a Phase I clinical trial de monstrating the feasibility of intraperitoneal radioimmunotherapy in p atients with refractory ovarian cancer using I-131-labeled monoclonal antibody OC125. We are now exploring the possibility of using caffeine to enhance the toxicity of I-131-irradiation in target cells. As an i n vitro model we tested this hypothesis using Chinese hamster ovary (C HO) cells exposed to I-131-labeled human serum albumin at various dose s (4 to 70 mu Ci/ ml) for 24 hr followed by 24 hr of incubation with c affeine. Cytotoxicity was measured by clonogenic survival and a nuclea r fragmentation assay. The results show that caffeine, at a concentrat ion of 7.7 mM, significantly enhances the cytotoxicity of I-131-irradi ation. (C) 1997 Academic Press.