Journal Article

Dieldrin Pretreatment Alters [<sup>14</sup>C]Dieldrin and [<sup>3</sup>H]7,12-Dimethylbenz[<i>a</i>]anthracene Uptake in Rainbow Trout Liver Slices

DUNCAN J. GILROY, CRISTOBAL L. MIRANDA, LISBETH K. SIDDENS, QUAN ZHANG, DONALD R. BUHLER and LAWRENCE R. CURTIS

in Toxicological Sciences

Volume 30, issue 2, pages 187-193
Published in print April 1996 | ISSN: 1096-6080
Published online April 1996 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/30.2.187
Dieldrin Pretreatment Alters [14C]Dieldrin and [3H]7,12-Dimethylbenz[a]anthracene Uptake in Rainbow Trout Liver Slices

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We previously demonstrated that pretreatment of rainbow trout with the organochlorine insecticide dieldrin altered in vivo disposition of a subsequent [14C]dieldrin dose. This was not explained by changes in total lipid content or the activity of common xenobiotic metabolizing enzymes. We hypothesized that dieldrin induced hepatic proteins responsible for organochlorine (OC) sequestration, transport, or excretion and that these changes reflected an adaptive response of trout to OC exposure. Here, uptake of 1.18 μM [14C]-dieldrin by precision cut liver slices was increased by dieldrin pretreatment of rainbow trout. Uptake of 0.118 and 1.18 μM [3H]-7,12-dimethylbenz[a]anthracene (DMBA) and efflux of 0.118 μM [3H]DMBA were significantly increased in slices from dieldrin pretreated trout. Liver slice uptake of 10 but not 1.18 μM [3H] estradiol and [3H]cholic acid was significantly increased by dieldrin pretreatment. There were no such significant differences for [3H]cholesterol, or [3H]cholesterol-oleate, or [3H]oleic acid uptake. Dieldrin pretreatment did not alter hepatic microsomal metabolism of [3H]DMBA or [14C]benzo[a]pyrene or content of six cytochrome P450 isozymes, as quantitated by Western blot analysis. These results provide further evidence that altered disposition of [14C]dieldrin and [3H]DMBA in dieldrin-pretreated trout was not explained by microsomal enzyme induction but reflected altered processes integral to hepatocellular transmembrane kinetics. These changes may have important implications for OC bioaccumulation by rainbow trout and demonstrate an interaction between dieldrin and DMBA in the absence of cytochrome P450 system induction.

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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