Daniel M. Shapiro

Antagonist Studies: Comparison of Desoxypyridoxine and Pyridoxine-Deficiency Therapy on Various Vitamin B6 Enzymes.

Summary 1. Mice receiving a vit. B6 deficient-high protein diet were observed to have significantly lower transaminase, dopa decarboxylase and cysteine desulfhydrase activities as compared to similar animals receiving an identical diet supplemented with pyridoxine. Cysteine desulfhydrase was the most sensitive to vit. B6 deprivation, followed by transaminase and dopa decarboxylase. 2. The administration of desoxypyridoxine to mice receiving an ad libitum stock diet containing adequate vit. B6 significantly decreased transaminase and dopa decarboxylase activity. However, cysteine desulfhydrase activity was uninhibited. 3. A possible explanation of the observed results is discussed, the potentialities of vitamin antagonists as precise chemotherapeutic agents being indicated.

Combination chemotherapy of cancer: potentiation of carcinostatic activity of 8-azaguanine by 6-formylpteridine.

Summary 1. 2-Amino-4-hydroxy-6-formyl pteridine (6-formylpteridine), although non-carcinostatic by itself, augmented the carcinostatic action of 8-azaguanine against a mammary adenocarcinoma. This effect was found to be dependent upon a time interval between the injection of 6-formylpteridine and 8-azaguanine. 2. 6-Formylpteridine inhibited the in vitro deamination of 8-azaguanine by tumor extracts. Pre-incubation of enzyme with inhibitor was found to be essential for maximal inhibition. 3. It was postulated that the enhanced carcinostatic effect observed in vivo could be due to inhibition of 8-azaguanine deamination by 6-formylpteridine, since the deaminated product (8-azaxanthine) is non-carcinostatic. We wish to express our appreciation to Dr. J. M. Ruegsegger of the Lederle Laboratories, Pearl River, N. Y., for supplies of 8-azaguanine, and to Drs. R. O. Roblin, Jr., and J. M. Smith, Jr., of the American Cyanamid Co., Stamford, Conn., and Bound Brook, N. J., for 6-formylpteridine. We wish to acknowledge the technical assistance of Miss R. Fugmann, Miss P. Hayworth, Miss A. Atti, and Mrs. E. Zanar.

In vitro Effect of Two Pantheine Analogues on Co-Enzyme A Requiring Systems.

Summary Omega-methylpantethine was observed markedly to inhibit sulfanilamide acetylation at concentrations which were ineffective against citrate formation in pigeon liver homogenates. With aliquots of the same homogenate. bis- beta-pantoylaminoethyl) disulfide was observed to inhibit citrate formation at concentrations which were ineffective against sulfanilamide acetylation. In either case, higher concentrations of these compounds were effective in inhibiting both systems.