The overall objective of the proposed research is to examine the compartmentalization of 2,4,5,2',4',5'-hexachlorobiphenyl (6-CB) in the white adipose tissue of rodents under normal conditions and during the physiological conditions of pregnancy and lactation which result in massive lipid mobilization. It has long been assumed that highly lipophilic chemicals such as 6-CB and DDT are dissolved in the """"""""well-stirred"""""""" triacylglycerol-rich central lipid globule of adipocytes. However, observed changes in the concentration of these chemicals within adipose tissue undergoing lipolysis suggest that persistent chemicals may become associated with different organelles over time or that different pools of triacylglycerol (and thus lipophilic chemical) exist which are more or less readily accessible for mobilization. Available data indicate that at least two distinct pools of lipid exist within the adipocyte - an actively metabolizing pool and a storage pool, and that the last lipid to be deposited within the adipocyte exists in a biochemical and/or anatomical pool that is mobilized first. The concentration effects observed with DDT and 6-CB, as well as studies examining the kinetics of two doses of 6-CB, suggest that these chemicals are also accumulated and released from adipocytes relative to the time of their administration. Thus, both lipid and these chemicals dissolved therein exhibit a """"""""last-in, first-out"""""""" phenomenon with respect to their deposition in and mobilization from adipose tissue.
Specific aims of the proposed investigations include: to determine whether the uptake, subcellular compartmentalization and release of 6-CB resembles that of glucose (glycerol) or free fatty acids in vivo and in isolated adipocytes; to examine the tissue distribution and subcellular compartmentalization of 6-CB in adipose tissue of rats pretreated at different time intervals with 14C-6-CB and unlabeled 6-CB; to investigate the relationship between time of administration of 6-CB and lipid deposition in vivo with their mobilization during pregnancy; and to study the redistribution of 14C-6-CB and unlabeled 6-CB which have been administered individually at different time intervals during the physiological massive lipid mobilization associated with pregnancy and lactation.
| Ring, B J; Seitz, K R; Gallenberg, L A et al. (1990) The effect of diet and litter size on the elimination of 2,4,5,2',4',5'-[14C]hexachlorobiphenyl from lactating mice. Toxicol Appl Pharmacol 104:9-16 |
| Gallenberg, L A; Ring, B J; Vodicnik, M J (1990) The influence of time of maternal exposure to 2,4,5,2',4',5'-hexachlorobiphenyl on its accumulation in their nursing offspring. Toxicol Appl Pharmacol 104:1-8 |
| Gallenberg, L A; Ring, B J; Vodicnik, M J (1987) Influence of lipolysis on the mobilization of 2,4,5,2'4',5'-hexachlorobiphenyl from adipocytes in vitro. J Toxicol Environ Health 20:163-71 |
| Gallenberg, L A; Vodicnik, M J (1987) The disposition and elimination of two sequential doses of 2,4,5,2',4',5'-hexachlorobiphenyl. Drug Metab Dispos 15:363-6 |
