This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mihich, E. Articles by Nichol, C. A. Search for Related Content PubMed PubMed Citation Articles by Mihich, E. Articles by Nichol, C. A.

Antitumor Effects of Methylglyoxal-bis(N⁴-methylthiosemicarbazone) and Their Potentiation in Pyridoxine-deficient Animals¹

( Department of Experimental Therapeutics, Roswell Park Memorial Institute, Buffalo 3, New York)

CH₃-GMS² and several compounds related to it were quite active against Sarcoma 180. The initial inhibition of the growth of this tumor by CH₃-GMS was followed by complete tumor regression in a significant number of cases. The incidence of delayed tumor regression caused by these drugs was greatly enhanced when the mice were fed a pyridoxine-deficient diet beginning on the day of tumor implantation. In addition to Sarcoma 180, other transplanted tumors sensitive to CH₃-GMS were Ehrlich carcinoma in solid form, Ridgway osteogenic sarcoma, adenocarcinoma 755, Walker carcinosarcoma 256, and Murphy-Sturm lymphosarcoma; 5 other tumors were not inhibited significantly. Combination of CH₃-GMS and azaserine was synergistic against Sarcoma 180.

The observed potentiation of the delayed effects of CH₃-GMS by pyridoxine deficiency may be explained by an action of this drug related to pyridoxine metabolism. Indeed CH₃-GMS was inactive against Sarcoma 180/B₆, a subline of Sarcoma 180 capable of growing in pyridoxine-deficient mice. Increased toxicity was seen in mice treated with combinations of CH₃-GMS and 4-DOP. In contrast, however, the level of vitamin B₆ in Sarcoma 180 was not decreased after treatment with CH₃-GMS. Moreover, the growth inhibition of Saccharomyces carlsbergensis induced by the drug was not prevented by pyridoxal, pyridoxine, or pyridoxamine. Thus the observed potentiation of the effects of CH₃-GMS by pyridoxine deficiency may be the expression of the combined effects of 2 independently acting and highly selective treatments.

¹ This investigation was supported in part by a research grant (CA-04130) from the National Cancer Institute, USPHS.

Received 11/ 6/64.