DDT is a long-lasting stimulator of drug metabolism in rats. This persistence of effect may be related to the long-lasting storage of DDT in body fat. Starvation of rats previously exposed to DDT can re-induce activation of hepatic drug metabolism, apparently by mobilizing DDT from body fat. Stimulation of hepatic drug metabolism can be demonstrated in rats maintained on diets containing as little as 5 ppm of DDT.
All analogs and metabolites of DDT which were tested were active as stimulators of hepatic drug metabolism in the rat. However, only DDE was equipotent as a stimulator. Metabolism of DDT beyond DDE may reduce the ability of the molecule to function as an activator of hepatic microsomal enzymes.
There may be a species difference in response of hepatic enzymes to DDT or its metabolites. A stimulation of hepatic drug metabolism by DDT or its analogs given as a single or repeated (daily for 3 days) injection could not be clearly demonstrated in mice. DDT and its analogs are the only insecticides tested which show this specific difference-chlordane and related structures markedly stimulate drug metabolism in both rats and mice.
Supported by a grant from the National Institutes of Health (GM-06034).