Hepatic and Intestinal Drug-Metabolizing Enzymes and the Tissue Distribution and Excretion of 14C-7,12-Dimethylbenz[a]anthracene in Rats Fed Diets Varying in Fat Concentration

Abstract

Diets containing 12 or 48% of calories from corn oil were fed to weanling Sprague-Dawley female rats for 28 days. Hepatic cytochrome P-450 content was higher with the high-fat diet, but the activities of cytochrome P-450 reductase, cytochrome c reductase, benzo[a]pyrene hydroxylase (BPH), and uridine-5'-diphosphoglucuronic acid (UDPGA) transferase were unchanged. There were no differences in small intestinal cytochrome P-450 or BPH attributable to diet. Additional rats given an oral dose of 14C-7,12-dimethylbenz[a]anthracene (14C-DMBA) after 28 days of feeding showed no effects of diet on the cumulative daily excretion of radioactivity from 14C-DMBA in the urine or feces over 72 h. However, rats fed the high-fat diet showed greater concentrations of radioactivity in the liver, kidney, adrenal, pituitary, breast, and adipose tissue at 4 h after dosing when compared to rats fed low-fat diets. The transiently higher tissue concentrations of 14C-DMBA in rats fed a high-fat diet prior to DMBA administration correlate with the enhancement of mammary cancer induction seen when high-fat diets are fed prior to administration of this carcinogen.