Metabolic mutagenicity

Thorgiersson SS, Glowinski IB, Mcmanus ME. Metabolism, mutagenicity and carcinogenicity of aromatic amines. In Hodgson E, Bend JR, Philpot RM, eds. Reviews in Biochemical Toxicology, Vol. 5. New York Elsevier-North Holland, 1983. 

Metabolism, Mutagenicity and Carcinogenicity (Refs 14, 33, 34, 39, 46 48). A number of metabolities of TNT were reported in the literature prior to 1974. These were apparently formed by the reduction of nitro groups or by oxidation of the methyl group, and possibly by condensation of hydroxylamine groups produced by reduction (Table 1). Moreover, an unidentified glucuronide was claimed as a major metabolite and was presumed to involve the... 

These pyrolysis products were also found in roasted tea and brandy-type alcoholic beverages (Sugimura and Sato, 1983). In addition, as a result of ethanol metabolism, mutagenic acetaldehyde is formed, while in coffee and tea caffeine, an inhibitor of DNA repair synthesis is present and may also contribute to cancer risk. 

Rice JE, Coleman DT, Hosted TJJ, et al. 1985b. On the metabolism, mutagenicity, and tumor-initiating activity of indeno(1,2,3-cd)pyrene. In Cooke M, Dennis AJ, eds. Polynuclear aromatic hydrocarbons Metabolisms, methods and metabolism. Proceedings of the Eighth International Symposium. Columbus, OH Battelle Press, 1097-1109. 

Figure 3. Microsomal metabolism of Trp-P-2 and AAF. HPLC profiles of organic solvent extracts of the metabolized mutagens. Rat livers (3-MC micro-some s) were used. HPLC was performed with a stainless steel reverse phase C-...

Rat, mouse Liver microsomes Induction by PB and 3-MC effects of induction on metabolism, mutagenicity, and carcinogenicity compared 136... 

Luczyhski, M.K. Gora, M. Brzuzan, P. Wilamowski, J. Kozik, B. 2005. Oxidative metabolism, mutagenic and carcinogenic properties of some polycyclic aromatic hydrocarbons. Environmental Biotechnology, v.l, p. 16-28. 

Chen HH, Sirianni SR, Huang CC. 1982. Sister chromatid exchanges in Chinese hamster cells treated with seventeen organophosphorus compounds in the presence of a metabolic activation system. Environ Mutagen 4 621-624. 

Pednekar MD, Gandhi SR, Netrawali MS. 1987. Evaluation of mutagenic activities of endosulfan, phosalone, malathion, and permethrin, before and after metabolic activation, in the Ames Salmonella test. Bull Environ Contam Toxicol 38 925-933. 

Although trichloroethylene itself may not be genotoxic, several of its metabolites are reactive and potentially genotoxic compounds (Miller and Guengerich 1982). Several isomers of 1,2-dichlorovinyl-cysteine, a product of trichloroethylene metabolism in the kidney, are mutagenic in the in vitro Ames assay... 

Greim H, Bonse G, Radwan Z, et al. 1975. Mutagenicity in vitro and potential carcinogenicity of chlorinated ethylenes as a function of metabolic oxirane formation. Biochem Pharmacol 24 2013-2017. 

These nltrosated amides, In contrast to the nltrosamlnes, do not require metabolic activation in order to alkylate cellular nucleophilic targets. Thus, many of these substances are directly acting mutagens and also carcinogens (38. ... 

It appears that considerable metabolism of nitrosamines takes place in the liver, from the finding that most of them are activated by rat liver microsomes to bacterial mutagens. However, relatively few nitrosamines induce liver tumors in rats. The most common target is the esophagus and a wide variety of nitrosamines induce tumors in this organ of rats, some only tumors of the esophagus, others tumors of other organs also. 

The experiments with deuterium-labeled nitrosamines illustrate two important points. One is that oxidation of nitrosamines takes place at more than one position in the molecule, and the outcome of the balance of such competing reactions probably is the determinant of carcinogenic potency. The second is that the reason for the failure of carcinogenesis to be mirrored in many cases by the microsomally activated bacterial mutagenicity is that there can be several metabolic steps leading to formation of the proximate carcinogenic agent and not all of these need necessarily involve microsomal enzymes. ... 

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