1,2-Dimethylhydrazine, binding

J. P. Cruse, M. R. Lewin and C. G. Clark, The effects of cholic acid and bile salt binding agents on 1,2-dimethylhydrazine-induced colon carcinogenesis in the rat. Carcinogenesis, 1981, 2, 439. 

Dimethylhydrazine is readily absorbed. It can be A -dein ethylated, yielding formaldehyde, and can be oxidized through several steps to yield methylazoxymethanol. It binds covalently to protein, DNA and RNA in many mammalian tissues. The colon of rats is a target organ for 1,2-dimethylhydrazine toxicity, where it can produce aberrant crypts. In developmental studies, it is embryo- and feto-toxic in rats. 

Dimethylhydrazine was also noted to be a good substrate for A-oxidation by amine oxidase (Prough 1973). In rat liver microsomes and S-9 fractions, both a nonenzymatic and an enzymatic component were identified for the metabolism of 1,1-dimethylhydrazine (Godoy et al. 1983). Formaldehyde was produced by both components, although the nonenzymatic component dominated the formation of a reactive protein-binding species. In contrast, rat liver slices metabolized 1,1-dimethylhydrazine to carbon... 

Several studies have shown that the reactive binding species generated by 1,1-dimethylhydrazine metabolism may be free radical intermediates. Rat liver microsomes and rat hepatocytes are capable of metabolizing 1,1-dimethylhydrazine to form methyl radical intermediates (Albano et al. 1989 Tomasi et al. 1987). The formation of tliese radicals was inhibited by the addition of inhibitors of cytochrome P-450 (SKF 525A, metyrapone, and carbon monoxide) and inhibitors of the flavin-containing monooxygenase system (methimazole). The formation of free radicals could also be supported nonenzymatically by the presence of copper ion (Tomasi et al. 1987). These data indicate that at least two independent enzyme systems and one nonenzymatic pathway may be involved in the metabolism of... 

Human Cultured bronchi Metabolism and binding of DMN and 1,2-dimethylhydrazine 177... 

Barbolt and Abraham[37] fed rats a diet containing 20% bran and administered 1,2-dimethylhydrazine (DMH) orally as well. There was 100% incidence of colon tumors in the control rats and 67% incidence in the bran-fed rats. The number of tumors per rat was 6.4 0.9 in the controls and 1.2 0.6 in the bran-fed group (p<0.001). There were no differences between the two groups in incidence of duodenal or cecal tumors. Thus, the effect of dietary bran was localized to the colon. Freeman et al.[38] obtained similar when they fed cellulose as the dietary fiber. Neither substance binds bile acids to any appreciable extent[10]. 

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