© 1986 Oxford University Press
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Mechanisms for the Release and Redistribution of 2,4,5,2',4',5'-Hexachlorobiphenyl (6-CB) from Hepatic Tissues in the Rat
Department of Pharmacology and Toxicology, Medical College of Wisconsin 8701 Watenown Plank Road, Milwaukee, Wisconsin 53226
Mechanisms for the Release and Redistribution of 2,4,5,2',4',5'-Hexachlorobiphenyl (6-CB) from Hepatic Tissues in the Rat. RAU, L. A., AND VODICNIK, M. J. (1986). Fundam Appl. Toxicol. 7, 494-501. The translocation of 6-[14C]CB from rat hepatic tissues to various media was studied employing in situ hepatic perfusion and primary hepatocyte culture techniques. 6-[14C]CB release from the hepatic tissues of female rats pretreated with 2 µCi 6-CB was dependent on the relative proportion of perfusate buffer components. Approximately 10% of hepatic 6-CB was released into buffer containing either 4% BSA or 4% BSA and 100 mg/dl exogenous human very low density lipoproteins (VLDL). 6-CB release was significantly increased under simulated hyperhpidemic conditions (400 mg VLDL/dl). Release declined when BSA was eliminated or replaced with Dextran. The distribution of 6-CB between the triacylglycerol (TG)-rich VLDL and the protein buffer components was found to be dependent on the ratio of TG:protein. Under hyperlipidemic perfusate conditions, approximately 83% of the 6-CB associated with the BSA fraction. Under normolipidemic conditions, 99% of the 6-CB associated with BSA. The concentration of 6-CB in TG was greatly increased under hyperlipidemic conditions. Thus, 6-CB distribution under simulated normolipidemic conditions could not be explained by saturation of the VLDL fraction. Approximately 15% of 6-CB was released from hepatocytes prepared from late pregnant or age-matched control rats. Eighty percent of 6-CB was associated with VLDL secreted from hepatocytes. The TG:protein ratio in culture media was approximately 1:6 while ratios of 1:20 or 1:600 occurred in the perfusion studies. These data suggest that 6-CB may be released from hepatic tissues in association with newly synthesized TG, but that once in the circulation, its distribution is dependent on the ratio of TG to protein present.