Summary.-Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes including nucleolar microsegregation and changes in the endoplasmic reticulum and mitochondria. 1-Methylhydrazine caused little morphological change in the liver. Tumours of the colon and kidney and also massive cystic hyperplasia of the liver were found in some of the rats and tumours of the anal margin and kidney in some of the mice, following single doses of 1,2-dimethylhydrazine. Incorporation of amino acids into rat liver proteins was inhibited by 1,2-dimethylhydrazine, which also caused disaggregation of hepatic polysomes. No effects on hepatic protein synthesis by 1,1 -dimethylhydrazine or 1-methylhydrazine were observed. Similarities between the effects of 1,2 -dimethylhydrazine, cycasin and dimethylnitrosamine are discussed.
1. Aminoacetonitrile, a lathyrogenic agent known to decrease the hepatotoxic action of dimethylnitrosamine, inhibited the metabolism of this compound by rats in vivo and by rat liver slices in vitro. 2. Methylation of nucleic acids in rat liver and kidney by dimethylnitrosamine in vivo was inhibited by treatment of the animals with aminoacetonitrile. 3. These findings are discussed in relation to the hypothesis that dimethylnitrosamine requires metabolism to exert its hepatotoxic and carcinogenic action.
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