Multiple tissue expression of AHR and arnt proteins in rats exposed to TCDD

This investigation examines the dose-response relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment and aryl hydrocarbon receptor (AhR) and aryl hydrocarbon nuclear translocator (Amt) protein induction in multiple tissues of female Sprague-Dawley rats. Rats received a single oral dose of 0.0 (corn oil vehicle), 0.01, 0.1, 0.3, 1.0, 10.0 or 30.0 ug [3H]TCDD/kg body weight and were sacrificed three days after dosing. Hepatic, renal and pulmonary cytosolic extracts were prepared and subjected to western blotting analysis with AhR and Arm antibodies. The data suggests that in all tissues examined the cytosolic AhR and Arm proteins are expressed dose-independently. Nuclear extracts were prepared from the liver and also revealed that regulation of the AhR and Amt proteins is unaffected by dose. Further analysis of the functionality of the ligand:AhR:Arnt heterodimer complex by western blotting and enzyme induction techniques showed that both cytochrome P4501A1 (CYP1A1) protein and ethoxyresorufin O-deethylase (EROD) activity (a marker for CYP1A1 activity) were dose-dependently expressed in the liver, lungs and kidneys. This is the first study to show that regulation of the AhR and Arnt proteins in multiple tissues of female Sprague-Dawley rats is unaffected by acute exposure to TCDD.