EFFECT OF DIETARY-PROTEIN CONCENTRATION ON YIELD OF MUTAGENIC METABOLITES FROM 1,2-DIMETHYLHYDRAZINE IN MICE

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (8) , 3674-3679
Abstract
The effects of varying dietary protein concentrations on the metabolism of 1,2-dimethylhydrazine (DMH) to mutagenic products by male C57BL/6 .times. C3H F1 mice were assayed by in vivo and in vitro methods. DMH and its metabolite, azoxymethane (AOM), did not increase the mutation frequency of Salmonella typhimurium (strain G-46) in vitro alone or in the presence of mouse liver homogenates capable of activating the promutagen dimethylnitrosamine. Methylazoxymethanol (MAM), another metabolite of DMH, was mutagenic in vitro without activation. S.c. administratin of DMH, AOM or MAM at dosages ranging from 0.2-0.8 mmol/kg of body wt caused dose-dependent increases in mutations of S. typhimurium in the host-mediated assay, and molar potencies increased progressively from DMH to AOM to MAM. S.c. or i.p. injections of AOM increased host-mediated mutagenesis within 20 min, while increases in mutagenesis by DMH required at least 1 h. When [14C]DMH was administered, [14C]azomethane was expired immediately, while 14CO2 began to appear 1 h after DMH administration. The percentage of administered [14C]DMH expired as azomethane varied inversely with dietary protein concentration, while AOM-induced host-mediated mutagenesis was directly proportional to dietary protein (P < 0.01). The percentage of DMH converted to mtuagenic end products was limited by losses of the volatile metabolite azomethane, especially in protein-deficient mice. Greater expiration of azomethane and decreased conversion of AOM to MAM, both seen with restriction of dietary protein, were associated with a smaller body burden of DMH metabolites.