title: Hepatic P450 enzyme activity, tissue morphology and histology of mink (Mustela vison) exposed to polychlorinated dibenzofurans.
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.
authors.affiliation: Department of Zoology, National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA. moorej42@msu.edu
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Moore
authors.forename: John L
authors.initials: JL
authors.lastname: Newsted
authors.forename: Markus
authors.initials: M
authors.lastname: Hecker
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Zwiernik
authors.forename: Scott D
authors.initials: SD
authors.lastname: Fitzgerald
authors.forename: Denise P
authors.initials: DP
authors.lastname: Kay
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.forename: Eric B
authors.initials: EB
authors.lastname: Higley
authors.forename: Lesa L
authors.initials: LL
authors.lastname: Aylward
authors.forename: Kerrie J
authors.initials: KJ
authors.lastname: Beckett
authors.forename: Robert A
authors.initials: RA
authors.lastname: Budinsky
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bursian
authors.forename: John P
authors.initials: JP
authors.lastname: Giesy
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000633:toxicity; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D008907:Mink / Q000502:physiology*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000633:toxicity; D011108:Polymers / Q000633:toxicity
chemical_list: D001572:Benzofurans; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D011108:Polymers; C016068:polychlorodibenzofuran; C078328:1,2,7,8-tetrachlorodibenzofuran; D003577:Cytochrome P-450 Enzyme System; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1