Chemo-immunotherapeutical studies on Dalton's lymphoma in mice using cisplatin and ascorbic acid: synergistic antitumor effect in vivo and in vitro.

Combined effects of ascorbic acid (vitamin C) and cisplatin on the growth of Dalton's lymphoma in C3H/He mice was investigated. Chemotherapy with sub-therapeutical dose (3 mg/kg) enabled to increase the survival time of the tumor bearing mice without any tumor free survivors. Ascorbic acid enhances the antitumor effect of cisplatin in vivo resulting in 60/70 day survivors along with tumor free survivors. Ascorbic acid also enhances the efficacy of low dose of cisplatin (5 micrograms/ml) in vitro. Tumor cells incubated with cisplatin and ascorbic acid, when injected into normal mice, exhibited inhibited growth resulting in an increased life span of tumor bearing mice and tumor free survivors. Inoculation of tumor cells incubated with cisplatin (5 micrograms/ml) and different concentrations (25 or 50 micrograms/ml) of ascorbic acid resulted in 30% tumor free mice which was not observed when concentration of cisplatin increased to 10 micrograms/ml in the medium. A possible cause of the enhancement of cisplatin-induced tumor growth inhibition may be the modulation of permeability of tumor cell membrane by ascorbic acid which increases the uptake of cisplatin into tumor cells, making less efficient the DNA repair machinery due to increased efficiency of adduct formation in DNA molecule. Possibly, this effect of ascorbic acid renders cisplatin more effective as an antitumor agent.