Abstract |
An attempt was made to distinguish different patterns of microsomal enzyme induction by phenobarbital, beta-naphthoflavone, and Aroclor 1254 on the biotransformation and excretion of the organochlorine insecticide lindane. Treated groups of six weanling female Sprague-Dawley rats, individually housed in metabolism cages, received diets containing either 500 ppm Aroclor 1254, 356 ppm phenobarbital, or 418 ppm beta-naphthoflavone. After 1 week all animals, except one group of controls, were dosed p.o. with 1.89 mg lindane (containing 1.63 mu Ci(U-(14)C) lindane). Twenty four hours later the rats were sacrificed and urine, feces, expired air, and tissue samples were taken for analysis of radioactivity. Hepatic cytochrome P-450 content, microsomal phospholipid content, and the enzyme activity involved in the dehydrogenation of lindane, the dechlorination of lindane, and the hydroxylation of the intermediate hexachlorocyclohexene were determined in vitro. Moreover, the effect of pre-treatment on the excretion of radioactivity and the distribution of eight lindane metabolites was examined. Even though the rate of lindane metabolism was unchanged by the beta-naphthoflavone pre-treatment, results of the study indicated that all three pre-treatments significantly altered lindane metabolism. The pre-treatments differed from one another in that they selectively altered specific metabolic pathways. |