Carcinogenicity, oxidative metabolism

Carcinogenicity, oxidative metabolism of xenoblotlc compounds by man, as major determinant, 33 Chemicals... 

N. and Pelkonen, 0. Oxidative metabolism of carcinogens by trout liver resulting in protein binding and mutagenicity. 

Electron-rich alkenes are the more reactive jr-bond snbstrates towards epoxidation by the electrophilic dioxiranes Some typical examples of these oxidations are snm-marized in Scheme 2. Since the resnlting epoxides are nsnally hydrolytically and ther-molytically qnite labile, snch oxidations are best carried ont with isolated dioxiranes. For example, the 8,9 epoxide of the well-known aflatoxin B, postnlated as potent carcinogen in the oxidative metabolism of this natural product, escaped numerous efforts to prepare it by conventional epoxidations because of its sensitivity towards hydrolysis . The synthesis of this labile epoxide was readily accomplished by employing a solution of the isolated DMD at room temperature (equation 2), and its mutagenicity unequivocally... 

Figure 5.14 Routes of oxidative metabolism of aflatoxin showing activation to an epoxide catalyzed by CYP1A2 and CYP3A4 and conjugation with glutathione catalyzed by a-GST. The 8,9-exoepoxide is the enantiomer, which binds extensively to DNA and is carcinogenic. The endoepoxide binds less readily. Abbreviation. a-GST, a-glutathione transferase.

Tomasi, A., Albano, E., Botti, B Vannini, V. (1987) Detection of free radical intermediates in the oxidative metabolism of carcinogenic hydrazine derivatives. Toxicol. Pathol., 15, 178-183... 

Many exogenous and endogenous carcinogens undergo oxidative metabolism by phase I enzymes, especially by the members of the cytochrome P450 (CYP)... 

Levin W, Wood A, Chang R, et al. 1982. Oxidative metabolism of polycyclic aromatic hydrocarbons to ultimate carcinogens. Drug Metab Rev 13 555-580. 

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