[Activation of environmental carcinogenic N-nitrosodialkylamines by model systems for metabolic oxidation].
Nitrosamines are environmental carcinogens, and their relevance to human cancer is highly suspected. Dialkylnitrosamines require activation through metabolizing enzymes before they become ultimate electrophilic active species. This review summarizes two model systems for metabolic oxidation of dialkylnitrosamines. One system utilizes porphyrin and oxidant as a model for shunt pathway in the metabolizing pathway of cytochrome P450, and the other one utilizes Fenton reagent. Porphyrin and oxidant activated nitrosodialkylamines into direct acting mutagen by releasing aldehydes. During the process the alkylating activity was observed and alcohols are formed from the alkylation of water. Fenton reagent, consisting of iron salt and hydrogen peroxide supplemented with copper salt, activated dialkylnitrosamines into mutagens of a novel type containing an oxadiazine ring as their proposed structures. These works with model systems open a new aspect into the elucidation of the mechanism of xenobiotic metabolism.
Mochizuki
M
M
Kyoritsu College of Pharmacy, Tokyo, Japan.
D000478:Alkylation; D002274:Carcinogens, Environmental / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System; D004052:Diethylnitrosamine / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide; D007501:Iron; D008954:Models, Biological; D016296:Mutagenesis; D009153:Mutagens; D016877:Oxidants; D010084:Oxidation-Reduction; D011166:Porphyrins; D015262:Xenobiotics
D002274:Carcinogens, Environmental; C045076:Fenton's reagent; D009153:Mutagens; D016877:Oxidants; D011166:Porphyrins; D015262:Xenobiotics; D004052:Diethylnitrosamine; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D007501:Iron