Differences in the Selective Antitumor Effects of 4-deoxypyridoxine and Dietary Pyridoxine Deficiency.

The effects of 4-deoxypyridoxine were contrasted with those of prolonged periods of dietary pyridoxine deficiency using Sarcoma 180 (S-180) as a test system. The drug was inactive against this tumor in animals fed complete diets. The antime tabolite markedly inhibited the growth of S-180 in mice fed a vitamin B6-deficient diet from the day of tumor implantation. Under such dietary conditions, which alone did not restrict the growth of the tumor, the drug was effective at levels as low as 1 mg/100 gm of diet. The inhibition of tumor growth caused by 4-deoxypyri doxine was not followed by regression of the tumor. The drug prevented the com plete regression of the tumor, which occurs in mice depleted of the vitamin from the 14th day prior to implantation, only when it was given during the week preceding, or that following, the day of implantation. 4-Deoxypyridoxine did not exert such an effect when it was given during the 2d week of tumor growth. The prevention of tumor regression by 4-deoxypyridoxine was consistent with the marked depression of lymphoid tissues exerted by this drug. The antimetabolite inhibited the growth of 5-180/B5, a subline capable of growing in pyridoxine-depleted mice, and of 5-180 ascites implanted subcutaneously, in contrast to the lack of effect of the dietary pyridoxine depletion on these tumors. The data reported herein indicate that pyridoxine antagonists differ among them selves with reference to their selective actions in the 5-180 system. Isonicotinic acid hydrazide alone was not very active either in inhibiting the growth of 5-180 or in preventing its regression in the deficient mice. Yet this compound markedly in creased the effects of 4-deoxypyridoxine when given in combination. Another an tagonist of vitamin B6, thiosemicarbazide, was very effective against S-180 regardless of the dietary condition and caused complete tumor regression. The incidence of regression was increased when thiosemicarbazide was administered to mice which were fed the deficient diet.