Mechanisms for the release and redistribution of 2,4,5,2′,4′,5′-hexachlorobiphenyl (6-CB) from hepatic tissues in the rat

• Published in: Fundamental and applied toxicology 1986-10, Vol.7 (3), p.494-501
• Main Authors: Rau, Lori A., Vodicnik, Mary Jo
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; Female; Lipoproteins, VLDL - biosynthesis; Liver - metabolism; Medical sciences; Perfusion; Polychlorinated Biphenyls - metabolism; Pregnancy; Proteins - metabolism; Rats; Rats, Inbred Strains; Tissue Distribution; Toxicology; Triglycerides - metabolism; Various organic compounds
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1016/0272-0590(86)90099-0

The translocation of 6-[ 14C]CB from rat hepatic tisses 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 hyperlipidemic 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.