Effects of Acute and Chronic DDT Administration on Hepatic Microsomal Drug Metabolism in the Rat.

Abstract

Summary DDT, 500 ppm, was fed in a lab chow diet to rats. Hexobarbital sleeping times and in vitro assays were measured after 2 weeks, 1, 2, 3 and 4 months on the diet to observe the effects of DDT on hepatic microsomal drug metabolizing enzyme activity. With the exception of aniline, which was not different from control at 2 weeks, 3 and 4 months, significant increases in rate of drug enzyme activity were seen at all times on the diet for the drugs studied. Shortened sleeping times paralleled these increases. Acute treatment of rats with DDT at 3 dose levels, each for 3 days, produced significant stimulatory effects on drug metabolism in vitro at both 1 and 8 days. Sleeping times were depressed at both times, although this depression was significant only at 1 day. In mice, acute injection of a single dose of DDT did not shorten hexobarbital sleeping times even at 3 days after treatment. Several of the organophosphorous insecticides were screened acutely with sleeping times in mice and produced either no effects or in several cases a prolongation of sleeping times. The proposal was made that the stimulatory effects of DDT on enzyme activity were due to its causing a proliferation of smooth surfaced endoplasmic reticulum in the liver cell, with a consequent increase in the amount of the drug metabolizing enzymes.