Potentiation of therapeutic effect of methanesulphonate and protection against its organ cytotoxicity by vitamin C in Ehrlich ascites carcinoma bearing mice.

Abstract

The effect of vitamin C upon the therapeutic index and side effects produced by methanesulfonate of aminoglycols (drug 864T, NSC 140117) had been evaluated in a laboratory system. The antitumor action of 864T, vitamin C and their combination were evaluated in Ehrlich ascites carcinoma (EAC) cells in vivo. Tissue toxicity was assessed using liver and intestinal DNA, RNA, protein contents and their synthesis as parameters. In addition, G-6-pase, 5-Nase and Alk, pase activity levels in both tissues were also measured. Drug 864T (200 mg/kg) produced 50 percent long-term survivors in tumor bearing mice in addition to 10 percent early mortality while in combination with vitamin C (250 mg/kg x 6), there was 80 percent long term survivors with no mortality related to drug toxicity. No toxicity, in all the parameters used, was observed when 864T was given in combination with vitamin C. Drug 864T alone produced a significant decrease in protein content of both liver and intestinal tissue while in combination with vitamin C normal levels were maintained. In addition, all the parameters used were either elevated or decreased by 864T treatment and returned to normal levels in combination with vitamin C. This study proved that vitamin C may be useful not only to potentiate the effect of anticancer drug 864T on the Ehrlich ascites carcinoma but also to antagonize the side effects of the drug.