CHICK MICROSOMAL OXIDASES . ISOLATION PROPERTIES AND STIMULATION BY EMBRYONIC EXPOSURE TO 1,1,1-TRICHLORO-2,2-BIS(P-CHLOROPHENYL)ETHANE

The optimum conditions for the activity of the chick liver microsomal oxidative N,N-dimethylaniline demethylase have been established. Reduced nicotinamide-adenine dinucleotide phosphate was required and was partially replaced by reduced nicotinamide-adenine dinucleotide. The enzyme was competitively inhibited by β-diethylaminoethyl diphenylpropylacetate. Michaelis constants in the absence and in the presence of β-diethylaminoethyl diphenylpropylacetate were determined for N,N-dimethyLaniline and N,N-dimethylaniline N-oxide. The data presented in this work demonstrate that the rate of N,N-dimethylaniline N-oxide demethylation by chick liver microsomal fraction is sufficiently high for the N-oxide to be considered as an intermediate in the oxidative demethylation of N,N-dimethylaniline. Ferrous ions activated the microsomal demethylase when incubated with nicotinamide-adenine dinucleotide phosphate and gave a greater oxidative reaction in the absence of nicotin amide-adenine dinucleotide phosphate. The microsomal fraction oxidized N,N-dimethylaniline when incubated with hydrogen peroxide generating system. The activity of this enzyme system in chicks hatched from eggs which had been injected with 1,1,1-trichloro-2,2- bis(p-chlorophenyl)ethane, 1,1-dichloro-2.2-bis(p-chlorophenyl)ethane, and 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene prior to the incubation has been determined. 1,1,1-Trichloro-2,2-bis(p-chlorophenyl)ethane and its major metabolites in the chick stimulated microsomal oxidative activity. However, there were no changes in the enzyme activity requirements or in the Michaelis constants both in the presence and absence of β-diethylaminoethyl diphenylpropylacetate. The ability of chick microsomal enzymes to dealkylate some carbamate insecticides was found to be increased by the embryonic exposure to 1,1,1-trichloro-2,2-bis(p-chlorophenyl›ethane, 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane, and 2,2-bis(p-chlorophenyl)ethylene. © 1968, American Chemical Society. All rights reserved.