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Metabolism of methylated analogs of aldrin and dieldrin by liver preparations from male and female rat
Authors:KA Hassall  A Dionyssiou-Asteriou  D Manning
Institution:1. Department of Physiology and Biochemistry, The University, Reading, England;2. Department of Physics, National Institute for Research in Dairying, Shinfield, Reading, England
Abstract:Analogs of aldrin and dieldrin have been synthesized, the molecules of which lack a methylene bridge but have two methyl groups attached to olefinic or oxirane ring carbon atoms. Their metabolism was studied using NADPH-supplemented 12,000g × 30-min supernate of livers from Wistar and CD strains of rats. The dimethylated olefin was not metabolized to its epoxide but was converted by supernate of liver from rats of both sexes to a labile hydroxylated metabolite. Exogenous NADPH increased the rate at which the olefin was metabolized, but concentrations of NADPH which increased the yield of the labile metabolite when added to female rat liver preparations decreased the yield when added to those from the male. This metabolite had a mass spectrum which was consistent with it being a hydroxymethyl derivative. The dimethylated epoxide was metabolized more slowly than the olefin, and a notable sex difference in the route of metabolism was evident. With supernate from livers of female rats the only metabolite detected by gas-liquid chromatography had a mass spectrum consistent with it being a ring-hydroxylated epoxide. Male rat liver supernate formed small quantities of the same compound, but the major metabolite had a mass spectrum indicative of a hydroxymethyl epoxide. No hydrolysis of the oxirane ring of the epoxide has been detected. The relevance of these results to the planned synthesis of cyclodienes of optimal biodegradability is mentioned.
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