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. 2009 Aug;57(2):416-25.
doi: 10.1007/s00244-008-9241-3. Epub 2009 May 21.

Hepatic P450 enzyme activity, tissue morphology and histology of mink (Mustela vison) exposed to polychlorinated dibenzofurans

Jeremy N Moore  1 , John L Newsted, Markus Hecker, Matthew J Zwiernik, Scott D Fitzgerald, Denise P Kay, Xiaowei Zhang, Eric B Higley, Lesa L Aylward, Kerrie J Beckett, Robert A Budinsky, Steven J Bursian, John P Giesy
Affiliations

Hepatic P450 enzyme activity, tissue morphology and histology of mink (Mustela vison) exposed to polychlorinated dibenzofurans

Jeremy N Moore et al. Arch Environ Contam Toxicol. 2009 Aug.

Abstract

Dose- and time-dependent effects of environmentally relevant concentrations of 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ) of 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,4,7,8-pentachlorodibenzofuran (PeCDF), or a mixture of these two congeners on hepatic P450 enzyme activity and tissue morphology, including jaw histology, of adult ranch mink were determined under controlled conditions. Adult female ranch mink were fed either TCDF (0.98, 3.8, or 20 ng TEQ(TCDF)/kg bw/day) or PeCDF (0.62, 2.2, or 9.5 ng TEQ(PeCDF)/kg bw/day), or a mixture of TCDF and PeCDF (4.1 ng TEQ(TCDF)/kg bw/day and 2.8 ng TEQ(PeCDF)/kg bw/day, respectively) for 180 days. Doses used in this study were approximately eight times greater than those reported in a parallel field study. Activities of the cytochrome P450 1A enzymes, ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-deethylase (MROD) were significantly greater in livers of mink exposed to TCDF, PeCDF, and a mixture of the two congeners; however, there were no significant histological or morphological effects observed. It was determined that EROD and MROD activity can be used as sensitive biomarkers of exposure to PeCDF and TCDF in adult female mink; however, under the conditions of this study, the response of EROD/MROD induction occurred at doses that were less than those required to cause histological or morphological changes.

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Figures

Fig. 1
Fig. 1
A single cyst consisting of squamous epithelial cells within the mandibular tissue at 4× (a) and at 20× (b). The arrow identifies the nest of cells proximal to the incisors
Fig. 2
Fig. 2
Effects of TCDF on liver (a) EROD and (b) MROD activity in mink exposed for up to 180 days via the diet. Data are presented as means with error bars indicating standard deviations. Different letters indicate significant differences (p < 0.05) between dose groups. Control n = 8 and each TCDF dose n = 6
Fig. 3
Fig. 3
Regression analysis between (a) EROD and (b) MROD activities and measured TCDF liver concentrations (ng TEQTCDF/kg, ww) of mink exposed via the diet for 90 and 180 days. Models in the figures represent the best fit of the data based on criteria given in the Materials and Methods section
Fig. 4
Fig. 4
Effects of PeCDF on liver (a) EROD and (b) MROD activities in mink exposed for up to 180 days via the diet. Data are provided as means with error bars indicating standard deviations. Different letters indicate significant differences (p < 0.05) between dose groups. Control n = 8 and each PeCDF dose n = 6
Fig. 5
Fig. 5
Regression analysis between (a) EROD and (b) MROD activities and measured PeCDF liver concentrations (ng TEQPeCDF/kg, ww) of mink exposed via the diet for 90 and 180 days. Models in the figures represent the best fit of the data based on criteria given in the Materials and Methods section
Fig. 6
Fig. 6
Effects of mixture of TCDF (4.1 ng TEQTCDF/kg bw/day) and PeCDF (2.8 ng TEQPeCDF/kg bw/day) on liver (a) EROD and (b) MROD activities in mink exposed for up to 180 days via the diet. Single TCDF and PeCDF doses are 3.8 ng TEQTCDF/kg bw/day and 2.2 ng TEQPeCDF/kg bw/day, respectively. Data are presented as means with error bars indicating standard deviations. Different letters indicate significant differences (p < 0.05) between treatments. Control n = 8, TCDF n = 6, PeCDF n = 6, and mixture n = 5
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