Effects of 4(5)-(3,3-dimethyl-1-triazeno)-imidazole-5(4)-carboxamide (NSC 45388) in proliferating rat tissues

Some effects of 4(5)-(3,3-dimethyl-1-triazeno)imidazole-5(4)-carboxamide (DIC) on normal proliferating tissues in rats were described. DIC caused marked but transient inhibition of labeled thymidine incorporation into DNA and presumably DNA synthesis of thymus, regenerating liver, spleen and small intestine. The inhibition was reversible and its duration dose dependent. When incorporation of precursors into DNA was markedly inhibited, no consistent concomitant effect on incorporation of precursors into RNA or protein was observed. Karyorrhectic cells appeared in the intestinal crypts as well as signs of necrosis in the thymus after administration of 125 mg/kg of DIC, but no significant pathologic changes were found in the spleen or regenerating liver. The relationship between selective inhibition of DNA synthesis and cytotoxic effect was observed.