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

We previously demonstrated that pretreatment of rainbow troutwith the organochlorine insecticide dieldrin altered in vivodisposition of a subsequent ¹⁴C]dieldrin dose. This was notexplained by changes in total lipid content or the activityof common xenobiotic metabolizing enzymes. We hypothesized thatdieldrin induced hepatic proteins responsible for organochlorine(OC) sequestration, transport, or excretion and that these changesreflected an adaptive response of trout to OC exposure. Here,uptake of 1.18 µM ¹⁴C]-dieldrin by precision cut liverslices was increased by dieldrin pretreatment of rainbow trout.Uptake of 0.118 and 1.18 µM ³H]-7,12-dimethylbenza]anthracene(DMBA) and efflux of 0.118 µM ³H]DMBA were significantlyincreased in slices from dieldrin pretreated trout. Liver sliceuptake of 10 but not 1.18 µM ³H] estradiol and ³H]cholicacid was significantly increased by dieldrin pretreatment. Therewere no such significant differences for ³H]cholesterol, or³H]cholesterol-oleate, or ³H]oleic acid uptake. Dieldrin pretreatmentdid not alter hepatic microsomal metabolism of ³H]DMBA or ¹⁴C]benzoa]pyreneor content of six cytochrome P450 isozymes, as quantitated byWestern blot analysis. These results provide further evidencethat altered disposition of ¹⁴C]dieldrin and ³H]DMBA in dieldrin-pretreatedtrout was not explained by microsomal enzyme induction but reflectedaltered processes integral to hepatocellular transmembrane kinetics.These changes may have important implications for OC bioaccumulationby rainbow trout and demonstrate an interaction between dieldrinand DMBA in the absence of cytochrome P450 system induction.