Pharmacokinetics of Lipophilic Agents Following Preexposure: Non-Cytochrome P-450Mediated Mechanisms

摘要

Low levels of lipophilic organochlorine compounds (OCs) are present in theenvironment. Despite the fact that there is no question regarding the toxicity of many of these compounds on an acute high dose basis, the chronic effects of low levels of these materials has not been adequately examined. Since the chemical properties of these materials make them incompatible with water, the cell must use specialized means for handling them. These include xenobiotic metabolizing enzymes, cytosolic binding proteins and lipid storage depots. The studies performed during the period of this grant were an attempt to characterize a pretreatment disposition response (PDR) system which is a portion of the cellular response to low levels of OCs. It is apparent from our studies that PDR is not due to changes in the total lipid content of cells but may be due to an alteration in cytosolic binding proteins. (jes)