GROWTH-CONTROL OF HUMAN COLON-TUMOR XENOGRAFTS BY ASCORBIC-ACID, COPPER, AND IRON

We have previously reported that ascorbic acid or a combination of asc orbic acid and cupric sulfate was able to inhibit the growth of human mammary and lung tumor xenografts in mice. In the present study, the 6 -day subrenal capsule assay method was used to investigate the effect of ascorbic acid, cupric sulfate and ferric chloride on the growth of a human colon tumor in mice, The method permits the observation of cha nges in the size of tumor fragments implanted beneath the renal capsul e of mice, without the effective intervention of the immune system. Re sults of dose-response experiments indicate that tumor growth was inhi bited when mice were fed a diet containing ascorbic acid (4 to 10 g/kg body weight/day) in combination with cupric sulfate (2 to 4 mg/kg bod y weight/day) or ferric chloride (2 to 8 mg/kg body weight/day), Ascor bic acid alone was much less effective, Copper and iron alone enhanced tumor growth. Since cupric or ferric ion is a catalyst for the oxidat ion of ascorbic acid, the results support the suggestion that the anti tumor mechanism involved a pro-oxidative effect of ascorbic acid on th e tumor. The observed antitumor activity is not due to the metabolism of ascorbic acid as a vitamin, but due to its chemical properties. The tumor-inhibiting effect seems to be a direct growth suppressive actio n of ascorbic acid oxidation and certain degradation products of ascor bic acid, which are formed in vitro and are not formed by the metaboli sm of ascorbic acid.