Potentiation of chemotherapy cytotoxicity following iododeoxyuridine incorporation in Chinese hamster cells.

This study reports on the potentiation of selected chemotherapy drugs following halogenated pyrimidine incorporation into cellular DNA. Exponentially growing cultures of Chinese hamster V79 cells were exposed to 10(-5) M IdUrd or BrdUrd for 17 hr (approximately 2 cell doublings). This exposure resulted in approximately 16% replacement of thymidine by IdUrd or BrdUrd in the cellular DNA. Following the IdUrd exposure, dose response curves were determined for a 1 hr exposure to the various drugs. IdUrd pre-treatment was shown to enhance the cytotoxicity of melphalan, adriamycin, cisplatin, and neocarzinostatin with enhancement ratios at 1% survival of 1.5, 1.8, 1.5, and 1.4 respectively. BrdUrd pre-treatment also enhanced cisplatin cytotoxicity. A combination of BrdUrd pretreatment, cisplatin, and X rays was shown to yield additive survival effects. These findings are discussed in the context of possible clinical application of local drug perfusion of tumor-containing organs.