Dietary and age influence on the pharmacokinetic parameters of 2-acetylaminofluorene in BALB/c mice.
In a chronic study conducted in our laboratories, we found dietary effects on 2-acetylaminofluorene (2-AAF) toxicity. To determine if the absorption, distribution, metabolism, or elimination of 2-AAF was altered by the age of the animals, diet, or 2-AAF treatment, pharmacokinetic studies were conducted on young (11 weeks) and old (78 weeks) BALB/c mice that had been fed one of four diets containing 4 or 24% fat and 12 or 24% protein. Blood, urine, and feces samples were obtained over a 31-hr period after dosing with 500 ppm 2-[14C]AAF (10 microCi/mouse). Total radioactivity was determined after combusting each sample in an oxygen atmosphere and counting in a scintillation counter. The data from each individual mouse was simulated on an analog-digital hybrid computer utilizing a two-compartment model with metabolism. The pharmacokinetic parameters within groups were analyzed to make statistical comparisons of the effects of diet, dose, age, and interactions among the groups. The pharmacokinetic predictions of a shorter elimination half-life, smaller area-under-the-curve value, and therefore a decreased exposure to 2-AAF and metabolites due to an increased elimination rate of the parent compound through the urine were consistent with the decreased pathological effects found from the chronic study for the low protein/low fat diet mice.
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000375:Aging; D000818:Animals; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology; D006207:Half-Life; D007408:Intestinal Absorption; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D014018:Tissue Distribution
D004041:Dietary Fats; D004044:Dietary Proteins; D015073:2-Acetylaminofluorene