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.
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.
Clinton
S K
SK
Division of Nutritional Sciences, University of Illinois College of Medicine, Urbana.
Visek
W J
WJ
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000493:pharmacokinetics*; D000818:Animals; D004041:Dietary Fats / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D007422:Intestines / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D004041:Dietary Fats; D015127:9,10-Dimethyl-1,2-benzanthracene; D006899:Mixed Function Oxygenases