Histological investigations on the liver-disturbing action of 2-methyl-4-amino-5-hydroxy-methylpyrimidine.

Abderhalden (1) injected the pyrimidine and thiazole moieties of thiamine in mice and rats with the object of investigating the biosynthesis of thiamine and observed the induction of running fits. Its cause was further proved to be the pyrimidine moiety, i.e., 2-methyl-4-amino-5-hydroxymethylpyrimidine (OMP). Makino and Sasaki (2) reported the induction of running fits after in jecting this compound in rats maintained on a watersoluble vitamin-deficient diet (DK diet), and named this compound "toxopyrimidine". Later, the Vitamin B Research Committee agreed to call it OMP instead of toxopyrimidine, which was to be used for a group of substances with similar pharmacological activi ties. Makino, together with Aramaki and Shintani (3) conducted studies on agents which would suppress the OMP-induced seizure in mice and found that vitamin B6 had this activity. On the basis of their results, vitamin B6 was called "atoxopyrimidine". Shintani (4) also observed in experiments rats that long-term administration of OMP resulted in a cessation of growth with charac teristic vitamin B6-deficient symptoms, which disappeared after administration of vitamin B6. Torigoe et al. (5) observed that the administration of OMP daily to mice with the basal diet resulted in a sharp loss of weight leading to death. Arai (6) and Shintani (4) found urinary excretion of xanthurenic acid in mice and rats after_ administration of OMP in tryptophan-loaded animals. Tani (7) failed to prevent the urinary excretion of xanthurenic acid by simply administering vitamin B6 alone but could completely prevent the excretion of the acid by giving vitamin B6 together with methionine. The disturbance in tryptophan metabolism suggests a liver-disturbing action of OMP and the effect of methionine is assumed to substantiate the view. The investigations on OMP which have hitherto been made, have dealt only with the running fits, the effect on the liver being entirely disregarded. The present study was conducted in an attempt to clarify the effect of OMP on the liver and the relationship of OMP to vitamin B6.