Azoxymethane

The following supplements the article on Azoxymethane in Vol 1, A670-L. It has been prepd by the electrochem redn of nitromethane in IN aq K hydroxide, with N-methylhydroxyl-amine as an intermediate, yield 60% (Ref 4). 

Azoxymethan reagiert mit Zinn(II)-chlorid in Salzsiiure zu 1,2-Dimethyl-hydrazinl. 

Azoxy-Verbindungen werden durch Pentacarbonyleisen3,4 bzw. Dinatrium-decacarbo-nyl-dichrom5 zu den entsprechenden Azo-Verbindungenreduziert. So erhalt manz. B. aus Hexafluor-azoxymethan 50% d.Th. Hexafluor-azomethan (Kp7,l0 -320)3 bzw. aus 2,2 -Dimethyl-azoxybenzol 65% d.Th. 2,2 -Dimethyl-azobenzol4. 

VERGHESE M, RAO D R, CHAWAN C B, WILLIAMS L L, SHACKELFORD L (2002) Dietary inului suppresses azoxymethane-induced aberrant crypt foci and colon tumors at the promotion stage in young fisher 344 rats. J. Nutr. 132 2809-2813. 

Sugie, S. et al., Inhibitory effects of plumbagin and jugloneon azoxymethane-induced intestinal carcinogenesis in rats. Cancer Lett., Ill, 111, 1998. 

Tanaka, T. et al., Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls astaxanthin and canthaxanthin during the post-initiation phase, Carcinogenesis, 16, 2957, 1995. 

McKeever, J., Qureshi, A., Gorey, T., Kay, E., Byrne, P. and Hennessey, T.P.J. (1992). Azoxymethane induced free radical activity in rat colon carcinoma. Gastroenterology 102, A378. 

Reddy BS, Mori H and Nicolais M. 1981. Effect of dietary wheat bran and dehydrated citrus fiber on azoxymethane-induced intestinal carcinogenesis in Fischer 344 rats. J Natl Cancer Inst 66 553-557. 

The application of flavonoids for the treatment of various diseases associated with free radical overproduction is considered in Chapter 29. However, it seems useful to discuss here some studies describing the activity of flavonoids under certain pathophysiological conditions. Oral pretreatment with rutin of rats, in which gastric lesions were induced by the administration of 100% ethanol, resulted in the reduction of the area of gastric lesions [157]. Rutin was found to be an effective inhibitor of TBAR products in the gastric mucosa induced by 50%i ethanol [158]. Rutin and quercetin were active in the reduction of azoxymethanol-induced colonic neoplasma and focal area of dysplasia in the mice [159], Chemopreventive effects of quercetin and rutin were also shown in normal and azoxymethane-treated mouse colon [160]. Flavonoids exhibited radioprotective effect on 7-ray irradiated mice [161], which was correlated with their antioxidative activity. Dietary flavones and flavonols protected against the toxicity of the environmental contaminant dioxin [162], Rutin inhibited ovariectomy-induced osteopenia in rats [163],... 

H. Narahara, M. Tatsuta, H. lishi, M. Baba, N. Uedo, N. Sakai, H. Yano and S. Ishiguro, K-ras point mutation is associated with enhancement by deoxycholic acid of colon carcinogenesis induced by azoxymethane, but not with its attenuation by all-trans-retinoic acid, Int. J. Cancer, 2000, 88(2), 157. 

B. A. Magnuson, N. Shirtliff and R. P. Bird, Resistance of aberrant crypt foci to apoptosis induced by azoxymethane in rats chronically fed cholic acid. Carcinogenesis, 1994, 15(7), 1459. 

AOM, azoxymethane MNNG, JV-methyl-JV -nitro-JV-mtrosoguamdine DMH, 1,2-dimethyl-hydrazine MNU, W-methyl-W-nitrosourea PhIP, 2-amino-l-methyl-6-phenylimidazole[4,5-b] pyridine sc, subcutaneous ip, intra-peritoneal ir, intra-rectal po, by mouth. 

M. J. Seraj, A. Umemoto, A. Kajikawa, S. Mimura, T. Kinouchi, Y. Ohnishi and Y. Monden, Effects of dietary bile acids on formation of azoxymethane-induced aberrant crypt foci in F344 rats. Cancer Lett., 1997, 115, 97. 

R. K. Wall, D. Stoiber, L. Nguyen, J. Hart, M. D. Sitrin, T. Brasitus and M. Bissonnette, Ursodeoxycholic acid inhibits the initiation and postinitiation phases of azoxymethane-induced colonic tumour development. Cancer Epidemiol. Biomarkers Prev., 2002, 11, 1316. 

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

K. Watanabe, T. Kamimori, S. Nakatsugi, T. Ohta, S. Ohuchida, H. Yamamoto, T. Maruyama, K. Kondo, S. Narumiya, T. Sugimura, K. Wakabayashi, Inhibitory effect of a prostaglandin E receptor subtype EP1 selective antagonist, ONO-8713, on development of azoxymethane-induced aberrant crypt foci in mice. Cancer Lett. 156 (2000) 57. 

CN173 Thorling, E.B., N. O. Jacobsen, and K. Overvad. The effect of treadmill exercise on azoxymethane-induced intestinal neoplasia in the male Fischer rat on two different high-fat diets. Nutr... 

Carcinogenesis inhibition. Decoction of the dried rhizome, in the ration of rats at a concentration of 20% of the diet, was equivocal vs azoxymethane-induced aberrant crypt focF . ... 

Caderni, G., Filippo, C.d., Luceri, C., Salvadori, M., Giannini, A., Biggeri, A., Remy, S., Cheynier, V., and Dolara, P., Effects of black tea, green tea and wine extracts on intestinal carcinogenesis induced by azoxymethane in F344 rats. Carcinogenesis, 21, 1965, 2000. 

Auf diese Weise sind Azoxymethan zu 55% und Azoxycyclopropan zu 34% zuganglich. 

Nigro, N.D., Singh, D.V., Campbell, R.L., and Sook, M. (1975). Effect of dietary beef fat on intestinal tumor formation by azoxymethane in rats, J. Natl Cancer Inst. 54,439. 

Bromophenylazo)-2/-toluene, 309 (2-BromophenyI)-iVM7-azoxy (2-hydroxy-5-methylbenzene), 358 p-Bromophenylurea, 138-139 Bromopropadiene, 17 2,3-Butadienoic add, 16 iV-l-Butenylpiperazine, 92 Butter yellow, hazard of, 291 f-Butylamine, oxidation of, 323 -Butyl azide, 269 f-Butyl-OlW-azoxymethane, 349 t-Butyl p-Bromophenylazoformate, 328 t-Butyl 2-(p-bromophenyl)carbazate, 328 H-Butyl carbamate, 238-239 t-Butyl carbamate, 241-243... 

In this reaction the source of the azoxy oxygen appears to be the nitroso group [6]. The preparation of t-butyl-OAW-azoxymethane (iV-methyl-A -t-butyldiazine jV -oxide) is an example of preparation of an unsymmetrical azoxy compound which is quite generally applicable. The structure assignment is based on NMR data. 

Preparation of t-Butyl-ONN-azoxymethane (N-Methyl-N -t-butyldiazine N-Oxide) [6, 9]... 

The simple chalcone 70 has distributed widely in Glycyrrhizin plants as a minor constituent, and its glycosides are main flavonoids of licorice as described in Chapter 1. Recently, Okuyama et al. reported inhibition effect of the chalcone (70) on azoxymethane-induced murine colon aberrant crypt foucus formation and carcinogenesis [116]. 

Dimethylhydrazine is metabolized by a sequence of oxidation steps, first dehydrogenation to azomethane, A -oxidation of this to azoxymethane and finally a C-oxidation to methylazoxymethanol (Fiala, 1975, 1977). This last metabolite decomposes to give the highly reactive methyldiazonium ion to which the carcinogenicity of the compound has been attributed. The sequential nature of these oxidation steps has been shown in the isolated perfused rat liver (Wolter Frank, 1982). Fiala (1977) showed that the C-oxidation of azoxymethane to methylazoxymethanol is catalysed by hepatic microsomes, while Schoental (1973) found that methylazoxymethanol was converted to the corresponding aldehyde by an NAD-dependent dehydrogenase. 

Fiala, E.S. (1977) Investigations into Ihc metabolism and mode of action of the colon carcinogens, 1,2-dimethylhydrazinc and azoxymethane. Cancer, 40, 2436-2445... 

Reddy, B.S., Narisawa, T., Wright, P, Vukusich, D., Weisburger, J.H. Wynder, E.L. (1975) Colon carcinogenesis with azoxymethane and dimethylhydrazine in germ-free rats. Cancer Res., 35, 287-290... 

No Azido, CaHs Ns 0, Diazido, CjlLNsO, Mononitro, CjHjNjOj, Dinitro, CaH N40s, or other nitro Derivatives of azoxymethane... 

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