Plasma Pyridoxal Phosphate Depletion by the Carcinostatic Procarbazine

Abstract

Summary

Intraperitoneal injection of the antitumor agent, procarbazine (MIH), produced a rapid and prolonged fall in plasma levels of pyridoxal phosphate in mice. A similar fall in plasma PALP followed administration of monomethylhydrazine, a postulated metabolite of MIH, and pyridoxal methylhydrazone. The effectiveness of the latter compound, a probable inhibitor of the pyridoxal kinase reaction, in depressing plasma PALP levels indicates a rapid turnover rate of plasma PALP. It appears likely that PALP depletion plays a role in the neurotoxic effects of this new chemotherapeutic agent.

The authors are grateful to Hoffmann LaRoche Inc., Nutley, New Jersey, for supplying N-isopropyl-α-(2-methylhydrazino)-p-toluamide hydrochloride (RO-4-6467/1).