COMPARISON OF INDUCTION-PATTERNS OF RAT HEPATIC MICROSOMAL MIXED-FUNCTION OXIDASES BY PESTICIDES AND RELATED CHEMICALS

Attempts were made to recognize different patterns of induction by pesticidal chemicals in the liver microsomes of rats. After treatment for 7 days with various chemicals, the animals were sacrificed and the pattern of induction in the liver was studied. By adopting a criterion for changes in cytochrome P-450 these pesticides were grouped into two groups, the chemicals which induce an increase in cytochrome P-450 and those which do not. Among the former compounds, tetrachlorodibenzo-p-dioxin and polychlorinated biphenyl were found to induce different types of cytochrome from the rest as judged by the drastic change in the 455:430-nm ratio, i.e., the pattern similar to that induced by 3-methylcholanthrene. In addition, six different drugs were used as substrates to recognize the differences among induction patterns of mixed-function oxidase activities. As a result, four basic groups of inducers were recognized. Phenobarbital-, DDT-, chlordane-, mirex- and kepone-induced liver microsomes were similar in their drug metabolizing activity. Dieldrin did not induce the metabolism of aminopyrine unlike all other inducers. N-Demethylase activities were not stimulated by either 3-methylcholanthrene or TCDD when ethylmorphine and benzphetamine were the substrates. Lindane and sesamex did not increase the level of cytochrome P-450, but stimulated the N-demethylation of benzphetamine and ethylmorphine. Even among the noninducers of cytochrome P-450, further quantitative and qualitative differences in NADPH2-cytochrome c reductase and mixed-function oxidase activities were evident which were useful parameters in distinguishing induction types. The above observations show that the qualitative changes in the drug metabolizing enzyme activities after treatment with pesticides appear to be group specific. © 1979.