Comparative toxicology of tetrachlorobiphenyls in mink and rats. I. Changes in hepatic enzyme activity and smooth endoplasmic reticulum volume

DeBorah M. Gillette, Richard D. Corey, William G. Helferich, James M. McFarland, Linda J Lowenstine, David E. Moody, Bruce D. Hammock, Lee R. Shull

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Abstract

Mink have been shown previously to be extraordinarily sensitive to polychlorinated biphenyls (PCBs) and related classes of halogenated hydrocarbons. This study explored several aspects of the acute response of mink to two purified tetrachlorobiphenyl (TCB) congeners and compared their response with that of the rat, a less sensitive and more thoroughly studied species. Young female pastel mink and young female Sprague-Dawley rats received three daily intraperitoneal injections with equimolar doses of either 2,4,2′,4′-TCB or 3,4,3′,4′-TCB, and were sacrificed after 7 days. Two control groups were used for each species; one was allowed free access to food and the other was pairfed to the 3,4,3′,4′-TCB treatment group. Rats remained clinically normal, while mink treated with 3,4,3′,4′-TCB developed severe anorexia, diarrhea, and melena. Both species had significant increases in hepatic cytochrome P-450 content and the characteristic shift in the spectral maxima from 450 to 448 nm in the 3,4,3′,4′-TCB- but not in the 2,4,2′,4′-TCB-treated animals. Rats but not mink had increased activities of several hepatic monooxygenases in response to both congeners while microsomal epoxide hydrolase was increased in rats after 2,4,2′,4′-TCB and in mink after 3,4,3′,4′-TCB. Significant increases in the relative volume of smooth endoplasmic reticulum within hepatocytes of 2,4,2′,4′-TCB-treated rats but not mink were confirmed by ultrastructural morphometry. Accumulation of both congeners was greater in adipose tissue than in the liver of either species. In both species, concentrations in adipose tissue were much greater for 2,4,2′,4′-TCB than for 3,4,3′,4′-TCB. PCB toxicosis in mink, as in other species, appeared to be dependent on isomeric arrangement of chlorine substituents. However, unlike other species, the toxicosis was not associated with biochemical or morphological evidence of hepatic enzyme induction. Moreover, the target organ of 3,4,3′,4′-TCB toxicosis in mink was the small intestinal mucosa.

Original languageEnglish (US)
Pages (from-to)5-14
Number of pages10
JournalFundamental and Applied Toxicology
Volume8
Issue number1
DOIs
StatePublished - 1987

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Mink
Smooth Endoplasmic Reticulum
Enzyme activity
Toxicology
Rats
Liver
Enzymes
Polychlorinated Biphenyls
Halogenated Hydrocarbons
Tissue
Epoxide Hydrolases
Adipose Tissue
Chlorine
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Melena
Animals
Enzyme Induction
Anorexia
Intestinal Mucosa

ASJC Scopus subject areas

  • Toxicology

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Comparative toxicology of tetrachlorobiphenyls in mink and rats. I. Changes in hepatic enzyme activity and smooth endoplasmic reticulum volume. / Gillette, DeBorah M.; Corey, Richard D.; Helferich, William G.; McFarland, James M.; Lowenstine, Linda J; Moody, David E.; Hammock, Bruce D.; Shull, Lee R.

In: Fundamental and Applied Toxicology, Vol. 8, No. 1, 1987, p. 5-14.

Research output: Contribution to journalArticle

Gillette, DeBorah M. ; Corey, Richard D. ; Helferich, William G. ; McFarland, James M. ; Lowenstine, Linda J ; Moody, David E. ; Hammock, Bruce D. ; Shull, Lee R. / Comparative toxicology of tetrachlorobiphenyls in mink and rats. I. Changes in hepatic enzyme activity and smooth endoplasmic reticulum volume. In: Fundamental and Applied Toxicology. 1987 ; Vol. 8, No. 1. pp. 5-14.
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N2 - Mink have been shown previously to be extraordinarily sensitive to polychlorinated biphenyls (PCBs) and related classes of halogenated hydrocarbons. This study explored several aspects of the acute response of mink to two purified tetrachlorobiphenyl (TCB) congeners and compared their response with that of the rat, a less sensitive and more thoroughly studied species. Young female pastel mink and young female Sprague-Dawley rats received three daily intraperitoneal injections with equimolar doses of either 2,4,2′,4′-TCB or 3,4,3′,4′-TCB, and were sacrificed after 7 days. Two control groups were used for each species; one was allowed free access to food and the other was pairfed to the 3,4,3′,4′-TCB treatment group. Rats remained clinically normal, while mink treated with 3,4,3′,4′-TCB developed severe anorexia, diarrhea, and melena. Both species had significant increases in hepatic cytochrome P-450 content and the characteristic shift in the spectral maxima from 450 to 448 nm in the 3,4,3′,4′-TCB- but not in the 2,4,2′,4′-TCB-treated animals. Rats but not mink had increased activities of several hepatic monooxygenases in response to both congeners while microsomal epoxide hydrolase was increased in rats after 2,4,2′,4′-TCB and in mink after 3,4,3′,4′-TCB. Significant increases in the relative volume of smooth endoplasmic reticulum within hepatocytes of 2,4,2′,4′-TCB-treated rats but not mink were confirmed by ultrastructural morphometry. Accumulation of both congeners was greater in adipose tissue than in the liver of either species. In both species, concentrations in adipose tissue were much greater for 2,4,2′,4′-TCB than for 3,4,3′,4′-TCB. PCB toxicosis in mink, as in other species, appeared to be dependent on isomeric arrangement of chlorine substituents. However, unlike other species, the toxicosis was not associated with biochemical or morphological evidence of hepatic enzyme induction. Moreover, the target organ of 3,4,3′,4′-TCB toxicosis in mink was the small intestinal mucosa.

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