Feeding rainbow trout diet containing low concentrations of the cyclodiene insecticide dieldrin increases biliary excretion of a challenge dose of [14C]dieldrin 300-700% and [3H]7,12-dimethylbenz[a]anthracene (DMBA) about 300%. This interaction occurs without evidence of induction of the cytochrome P-450 system, UDP-glucuronyltransferase, or glutathione S-transferases. Precision cut liver slices from dieldrin-fed trout accumulate about two-fold more [14C] dieldrin from medium than slices from control fish. Liver slices from dieldrin fed trout exhibit slightly increased uptake but more markedly stimulated efflux of [3H]DMBA. Preliminary immunohistochemical studies provide no evidence for induction of a multidrug resistance (mdr)-like protein in liver of dieldrin fed rainbow trout. Column chromatography indicates dieldrin increases [3H]DMBA and [3H]benzo[a]pyrene binding protein(s) in rainbow trout hepatic cytosol. The working hypothesis for the proposed research is that dieldrin induces hepatic binding protein(s) important in biliary excretion of anionic metabolites of lipophilic xenobiotics. The rainbow trout is emerging as useful model in research on chemical carcinogenesis and as a sentinel species in assessing status and extent of water contamination. Identifying a binding protein which may be rate limiting in hepatic elimination of some lipophilic xenobiotics would advance mechanistic explanations of their disposition in the rainbow trout model. The objectives for this proposal are to: (1) purify a dieldrin-inducible DMBA binding protein from rainbow trout cytosol; (2) conduct competitive binding assays with this protein; and (3) determine the N-terminal sequence of 20-30 amino acids for this protein.
| Curtis, L R; Hemmer, M J; Courtney, L A (2000) Dieldrin induces cytosolic [3H]7, 12-dimethylbenz[a]anthracene binding but not multidrug resistance proteins in rainbow trout liver. J Toxicol Environ Health A 60:275-89 |
