Methylazoxymethanol , effect

Kate K, Kawai T, Fuji M, et al. 1985. Enhancing effect of preadministration of carbon tetrachloride on methylazoxymethanol acetate-induced intestinal carcinogenesis. J Toxicol Sci 10 289-293. 

Table 9. Effect of methylazoxymethanol acetate on Sprague-Dawley and Lobund Wistar rats...

Table IV. Effect of dietary protein concentration on host mediated mutagenicity of dimethylhydrazine (DMH), azoxy-methane (AOM) and methylazoxymethanol (MAll) in C57BL/6 x C3HF1 male mice...

Of critical concern is the possibility that developmental exposure may result in an acceleration of age-related decline in function. Animal studies have demonstrated that developmental exposure to neurotoxicants such as methylmercury, methylazoxymethanol, and ethanol may cause few or no neurotoxic effects in young animals, but marked effects in ageing animals. Investigations of effects in ageing animals are not included in regulatory guidelines. 

Luthman J, Eriksdotter-Nilsson M, Jonsson G (1990) Structural and neurochemical effects in mouse cerebellum following neonatal methylazoxymethanol and 6-hydroxydopamine treatment. Int J Dev Neurosci 5 107-118. 

Since reactive intermediates are produced as a result of the metabolism of hydrazines, the administration of inhibitors of the cytochrome P-450 or the flavin-containing monooxygenase system may offer some protective effect. For example, disulfiram, an inhibitor of cytochrome P4501 lEl (Guengerich et al. 1991), decreased the oxidation of azomethane (a metabolite of 1,2-dimethylhydrazine) to azoxymethane, and the further oxidation of azoxymethane to methylazoxymethanol (Fiala et al. 1977). The inhibition of... 

Soc. Japan 19, 77 (1955), C.A. 50, 13756g (1956) Riggs. Chem. Ind. (London) 1956, 926 Matsumoto, Strong, dtch, Biochem. Bjopiiy,. 101, 299 (1963). Biological effects, metabolism and mechanism of action of cycasin and its aglycone, methylazoxymethanol Spate, Ann. N. Y. dead. Sci 163, 848 (1969). Structure Korsch, Riggs, Tetrahedron... 

Concerns have been raised about the genotoxicity of the individual components of Stoddard solvent. Frequency of mutations induced by methylazoxymethanol (MAM), a complete carcinogen in several species, was increased (p<0.05) in V79 Chinese hamster cells by n-decane, while treatment with this alkane alone did not cause mutagenesis (Lankas et al. 1978). This suggests that n- decane may be a promoter. Further study is needed to determine whether the effects observed with individual components would also occur in the Stoddard solvent mixture. 

FIGURE 3. Effect of time in hours between treating the mice with cyasin or its aglycone methylazoxymethanol and the indicator microorganisms on the mutation frequency. Mutation frequency is the ratio of prototrophs to auxotrophs among the Salmonella after 2 hr in the host. 

We have been interested in the effect of poly(ADP-ribosyl)ation on chemical carcinogenesis in vivo. The system used was the induction of hepatocarcinogenesis by methylazoxymethanol acetate (MAM acetate) in the small fish Medaka", Oryzias latipes. Medaka was selected as a suitable model animal for the following reasons It is easy to breed, adapts to a wide range of temperatures, is easy to sexually differentiate, has a short reproductive cycle, and is available as a pure strain. In addition, continuous administration to Medaka of the drug is possible by simply dissolving it in tank water. 

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