Azoxymethane
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| Surname | Azoxymethane | |||||||||||||||
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| Molecular formula | C 2 H 6 N 2 O | |||||||||||||||
| Brief description |
colorless liquid |
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| properties | ||||||||||||||||
| Molar mass | 74.08 g mol −1 | |||||||||||||||
| density |
0.991 g cm −3 |
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| boiling point |
97-99 ° C |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||
Azoxymethane (AOM) is a carcinogenic liquid and a derivative of azomethane .
properties
Azoxymethane has a flash point of 24 ° C.
Carcinogenic effect
Azoxymethane is very carcinogenic . In rodents, the administration of azoxymethane specifically induces the development of colorectal carcinomas . The lesions correspond to colon carcinogenesis in humans. For this reason, azoxymethane is used in oncology to induce colon cancer in laboratory animals . For this purpose, the compound is usually administered subcutaneously or intraperitoneally .
In the liver , azoxymethane is formed as a metabolic product through the oxidation of 1,2-dimethylhydrazine (DMH). DMH is thus the procarcinogen of azoxymethane. Azoxymethane is further converted to methyl azoxymethanol (MAM) in the liver . MAM is glucuronized and ultimately reaches the intestine via the bile . The enzyme β-glucuronidase present there hydrolyzes the conjugate back to MAM. The β-glucuronidase can come from the bacteria of the intestinal flora as well as from the intestinal epithelial cells . Methylazoxymethanol decomposes at 37 ° C with a half-life of 12 hours into N-methylnitrosamine and a methyl radical . The methyl radical can alkylate the DNA in the cell nucleus to 6-O-methylguanine . If the damage to the DNA is not repaired, the methylation during replication leads to a transition from guanine to adenine , which is caused by a misbinding of 6-O-methylguanine with thymine .
synthesis
Azoxymethane can be produced electrochemically from nitromethane , for example .
Individual evidence
- ↑ a b c d e f Datasheet Azoxymethane from Sigma-Aldrich , accessed on May 12, 2017 ( PDF ).
- ^ H. Druckrey : Production of colon carcinoma by 1,2-dimethylhydrazines ans axozyalkanes. In: Carcinoma of the colon and antecedent epithelium. Walter J. Burdette (Editor), WJ Thomas Books, Springfield, 1970, pp. 578-579.
- ^ JH Weisburger and ES Fiala: Experimental colon carcinogens and their mode of action. In: Experimental colon carcinogenesis H. Autrup (Editor), Boca Raton, 1983, pp. 27-50.
- ↑ A. Bissahoyo, RS Pearsall, K. Hanlon, V. Amann, D. Hicks, VL Godfrey, DW Threadgill: Azoxymethane is a genetic background-dependent colorectal tumor initiator and promoter in mice: effects of dose, route, and diet. In: Toxicol Sci 88, 2005, pp. 340-345. PMID 16150884
- ↑ HT Nagasawa, FN Shirota, H. Matsumoto: Decomposition of methylazoxymethanol, the aglycone of cycasin, in D 2 O. In: Nature 236, 1972, pp. 234-235. PMID 4553643
- ↑ DC Herron and RC Shank: DNA methylation during chronic administration of 1,2-dimethylhydrazine in a carcinogenic regimen. In: Carcinogenesis 3, 1982, pp. 857-860. PMID 7127668
- ^ AE Pegg and TL Byers: Repair of DNA containing O6-alkylguanine. In: FASEB J 6, 1992, S: 2302-2310. PMID 1544541 (Review)
- ↑ C. Fähndrich: Effect of apple juice on colon carcinogenesis and its modulation by growth factors in animal experiments. (PDF; 1.8 MB) Dissertation, University of Veterinary Medicine Hannover, 2005.
- ↑ PE Iversen: Organic Electrosyntheses, IV. Representation of azoxymethane and 1,2-dimethylhydrazine from nitromethane and of azoxycyclopropane from nitrocyclopropane. In: Chemischeberichte 104, 1971, pp. 2195-2198. doi : 10.1002 / cber.19711040719