Adipose tissue content as a modifier of the tissue distribution, biological effects, and excretion of a hexachlorobiphenyl in C57BL/6J and DBA/JBOMf mice.

C57BL/6J (C57) and DBA/JBOMf (DBA) mice were used to study the role of adipose tissue as a modifier of tissue distribution, biological effects, and elimination of a lipophilic foreign chemical, 2,4,5,2',4',5'-hexachlorobiphenyl (HCB). As an indication of biological potency of the model compound, the activities of hepatic drug-metabolizing enzymes were determined. DBA mice contained twice as much body fat as C57 mice. Since the highly lipophilic HCB was primarily sequestered by the adipose tissue, DBA mice required greater doses of HCB than did C57 mice to reach similar tissue levels of the chemical. Accordingly, greater HCB doses were required by DBA mice for elevation of drug-metabolizing enzyme activities. Phenobarbital elevated enzyme activities in a similar way in both mouse strains. When the dietary intake of DBA mice was restricted, the body fat content decreased from 15% to 5% of body weight during 1 week. In these animals the tissue accumulation of HCB and enzyme induction resembled the situation in C57 mice fed ad libitum. Highest elevations were seen in the activities of 7-ethoxycoumarin-O-deethylase and arylhydrocarbon hydroxylase (EC 1.14.14.2). In addition, the activity of epoxide hydrolase (EC 3.3.2.3) was increased, whereas glutathione S-transferase as well as UDP-glucuronosyltransferase (EC 2.4.1.17) activities remained unchanged. The abundant adipose tissue content played no role in the nonresponsiveness of DBA mice to 3-methylcholanthrene since, in contrast to C57 mice, no changes in enzyme activities were detected in DBA mice deprived of food, even after large doses of 3-methylcholanthrene. The adipose tissue content also affected the rate of elimination of HCB. DBA mice excreted smaller quantities of HCB than did C57 mice after equal doses. When, however, fasted DBA mice received HCB, they excreted it at rates similar to those of C57 mice fed ad libitum. In C57 mice, concomitant to the elevation of monooxygenase activities, there was an increase in the rate of excretion of HCB. No such elevation could be seen after a dose that was too small to elevate enzyme activities.