Moore Jeremy N, Newsted John L, Hecker Markus, Zwiernik Matthew J, Fitzgerald Scott D, Kay Denise P, Zhang Xiaowei, Higley Eric B, Aylward Lesa L, Beckett Kerrie J, Budinsky Robert A, Bursian Steven J, Giesy John P
Department of Zoology, National Food Safety and Toxicology Center, Michigan State University, East Lansing, MI 48824, USA.
Arch Environ Contam Toxicol. 2009 Aug;57(2):416-25. doi: 10.1007/s00244-008-9241-3. Epub 2009 May 21.
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.
在可控条件下，测定了环境相关浓度的2,3,7,8 - 四氯二苯并呋喃（TCDF）、2,3,4,7,8 - 五氯二苯并呋喃（PeCDF）或这两种同系物的混合物的2,3,7,8 - 四氯二苯并 - p - 二噁英当量（TEQ）对成年养殖水貂肝脏P450酶活性和组织形态（包括颌组织学）的剂量和时间依赖性影响。成年雌性养殖水貂分别喂食TCDF（0.98、3.8或20 ng TEQ(TCDF)/kg体重/天）或PeCDF（0.62、2.2或9.5 ng TEQ(PeCDF)/kg体重/天），或TCDF和PeCDF的混合物（分别为4.1 ng TEQ(TCDF)/kg体重/天和2.8 ng TEQ(PeCDF)/kg体重/天），持续180天。本研究中使用的剂量比平行野外研究中报告的剂量大约高八倍。暴露于TCDF、PeCDF和两种同系物混合物的水貂肝脏中，细胞色素P450 1A酶乙氧基异吩恶唑酮 - O - 脱乙基酶（EROD）和甲氧基异吩恶唑酮 - O - 脱乙基酶（MROD）的活性显著更高；然而，未观察到明显的组织学或形态学影响。已确定EROD和MROD活性可作为成年雌性水貂暴露于PeCDF和TCDF的敏感生物标志物；然而，在本研究条件下，EROD/MROD诱导反应发生的剂量低于引起组织学或形态学变化所需的剂量。
