Dieldrin induces cytosolic [3H]7, 12-dimethylbenz[a]anthracene binding but not multidrug resistance proteins in rainbow trout liver.
Previously it was demonstrated that biliary excretion of a single dose of [14C]dieldrin or [3H]7, 12-dimethylbenz/alanthracene (DMBA) was stimulated up to 700% and 300%, respectively, in rainbow trout fed 0.3-0.4 mg dieldrin/kg/d for 9-12 wk. This was not explained by increased activities of hepatic microsomal xenobiotic-metabolizing enzymes or increased amounts of any of six cytochrome P-450 isozymes quantitated by Western blots. It was hypothesized that stimulated excretion was explained by induction of (1) cytosolic binding proteins that facilitated intracellular trafficking of DMBA to sites of metabolism, or (2) ATP-dependent proteins that transport xenobiotic metabolites from liver to bile. Binding of 15 and 60 nmol [3H]DMBA/mg protein increased about 200% in hepatic cytosol from dieldrin-fed fish. A 50-fold molar excess of unlabeled DMBA reduced binding of 15 nmol [3H]DMBA/mg protein (nonspecific binding) by the same amount in cytosol from control and dieldrin-fed fish, indicating that dieldrin induced specific binding. Liver sections from control and dieldrin-fed fish were treated with multidrug resistance (MDR) protein monoclonal antibodies C494, C219, and JSB-1, and polyclonal antibody MDR Ab-1. There were no marked differences in optical densities of immunohistochemical staining near bile canaliculi of control and dieldrin-fed fish. Induction of xenobiotic binding capacity in cytosol of dieldrin-fed rainbow trout at least partially explained altered DMBA disposition in fish pretreated with this cyclodiene insecticide.
Department of Environmental Health, East Tennessee State University, Johnson City, USA. larry.curtis@orst.edu
L R
LR
Curtis
M J
MJ
Hemmer
L A
LA
Courtney
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics; D018435:ATP Binding Cassette Transporter, Subfamily B / Q000032:analysis; D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D004026:Dieldrin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D017686:Oncorhynchus mykiss / Q000378:metabolism*
D018435:ATP Binding Cassette Transporter, Subfamily B; D015127:9,10-Dimethyl-1,2-benzanthracene; D004026:Dieldrin