3,4,3',4'-Tetrachlorobiphenyl distribution and induced effects in the rat adrenal gland. Localization in the zona fasciculata.
The distribution of radiolabeled 3,4,3',4'-tetrachlorobiphenyl (TCB) and TCB-induced effects on serum and adrenal gland retinoid content, and adrenal gland morphology was studied by liquid scintillation counting, high performance liquid chromatography, light microscopic autoradiography, and transmission electron microscopy. Adult, female WAG/Rij rats received a single intraperitoneal injection of either vehicle (corn oil), 15 mg TCB/kg, or 200 mg TCB/kg body weight and were sacrificed (N = 3 per group) at 1, 3, 7, and 14 days after treatment. One rat of the high dose group that was sacrificed at each sampling time had received radiolabeled compound (containing 1.85 mCi of 3H-TCB). At day 1, the adrenal gland had the greatest concentration of radioactivity (dpm x 10(-6)/gm wet tissue) of any organ examined. There was a selective distribution of radiolabeled compound to the zona fasciculata accompanied by morphometric evidence of hypertrophy of the zona fasciculata. The vast majority of 3H-TCB present in the adrenal gland was parent compound at all time periods. Serum retinol content was significantly decreased in the high dose group by 61 and 54% at days 3 and 7, respectively. No significant decrease in adrenal gland retinoid content occurred at any time in this study, but in contrast, adrenal gland retinol and retinyl palmitate content was increased. Serum cortisol levels were transiently decreased in the high dose group. Ultrastructural alterations were only observed in cells of the zona fasciculata. Predominant changes included mitochondrial hypertrophy and concentric whorling lamellar arrays of the membranes of the outer mitochondrial compartment and mitochondrial cristae. The results of this study indicate that the rat adrenal gland is an early target organ after TCB intoxication, and that there is an early and selective distribution of TCB in the rat adrenal gland accompanied by morphologic alterations in the sites of compound localization. The results further suggest that the observed morphologic changes did not result from hypovitaminosis A.
Durham
S K
SK
Department of Toxicology and Pathology, Hoffmann-La Roche, Nutley, New Jersey.
Brouwer
A
A
D000818:Animals; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D006984:Hypertrophy; D008854:Microscopy, Electron; D011078:Polychlorinated Biphenyls / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014801:Vitamin A / Q000097:blood; D015383:Zona Fasciculata / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D014801:Vitamin A; D011078:Polychlorinated Biphenyls; D006854:Hydrocortisone; C028451:3,4,3',4'-tetrachlorobiphenyl