Coplanar PCBs Health Effects in the Rat: Dose-Effect Relationships and Reproductive Toxicity Endopoint

共面 PCB 对大鼠的健康影响：剂量效应关系和生殖毒性端点

• 批准号: 11460147
• 负责人: AKAHORI Fumiaki
• 金额: $ 9.02万
• 依托单位: Azabu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11460147/
• 关键词: coplanar PCBs; reproductive toxicity; endpoint; hepatic cytochrome P450; components of complement

(1) Single injection of 10 or 100 μg/kg of PCB 126 on gestation day (GD) 15 to the dams delayed vaginal opening (VO) of their offspring significantly. In contrast, daily exposure to PCB 126 delayed VO only at a dose of 3 μg/kg/day, although cumulative doses of PCB 126 until chorionic gonandotropin (CG) 15 in the 1 μg/kg/day-group were estimated as much larger than 10 μg/kg. In addition, while a single injection of PCB 126 reduced the number of corpus lutea (CL), daily exposure to 1μg/kg/day did not alter it. These findings indicate that daily exposure may diminish effects of PCB 126 on female offspring as compared to single injection on GD 15. (2) The effects of Co-PCBs on CYP1A1, CYP1A2 and CYP2B1/2 mRNA expression were investigated by semi quantitative RT-PCR analysis in rats. In utero exposure to PCB126 (3μg/kg) or PCB169 (30 μg/kg) induced CYP1A1 and CYP1A2 mRNA expression levels in the liver of both male and female offspring. Exposure to PCB126 (30 μg/kg) or PCB169 (30 μg/kg) to pregnant rats induced CYP1A1, CYP1A2 and CYP2B1/2 mRNA expression levels in the placenta. (1) Proteins in the plasma of the (1-, 3-, 6-, and 15-week-old) rats, which were exposed to PCB126 or PCB169 in the viviparous phase, were analyzed by micro 2-dimensional electrophoresis. The influence of exposure to Co-PCBs on complement components (C3 and C4) in the plasma was observed in the 6- and 15-week-old rats, which were prenatally exposed to Co-PCBs. When toxicity for reproduction and development was considered from the aspect of the influence of Co-PCBs on a living body as an end point, the inactive amount was estimated to be 1 μg/kg. (4) It was also revealed that the exposure in the viviparous phase and milk-mediated exposure of neonates influenced expression of CYP1A1, CYP1A2, and CYP2B1/2 mRNA in the liver and dynamic changes in the complement system of proteins in the plasma.

(1)在妊娠第15天(GD)向母鼠单次注射10或100μg/kg的PCB 126，显着延迟其后代的阴道开放(VO)。相比之下，每日暴露于 PCB 126 仅在剂量为 3 μg/kg/天时延迟 VO，尽管在 1 μg/kg/天组中 PCB 126 直至绒毛膜促性腺激素 (CG) 15 的累积剂量估计远大于 10 μg/kg。此外，虽然单次注射 PCB 126 会减少黄体 (CL) 的数量，但每天暴露于 1μg/kg/天并不会改变它。这些结果表明，与 GD 15 上单次注射相比，每日暴露可能会减弱 PCB 126 对雌性后代的影响。 (2) 通过大鼠半定量 RT-PCR 分析研究了 Co-PCB 对 CYP1A1、CYP1A2 和 CYP2B1/2 mRNA 表达的影响。在子宫内暴露于 PCB126 (3μg/kg) 或 PCB169 (30 μg/kg) 会诱导雄性和雌性后代肝脏中 CYP1A1 和 CYP1A2 mRNA 的表达水平。怀孕大鼠暴露于 PCB126 (30 μg/kg) 或 PCB169 (30 μg/kg) 会诱导胎盘中 CYP1A1、CYP1A2 和 CYP2B1/2 mRNA 表达水平。 (1)通过显微二维电泳分析胎生期暴露于PCB126或PCB169的大鼠(1周龄、3周龄、6周龄和15周龄)血浆中的蛋白质。在产前接触 Co-PCB 的 6 周和 15 周龄大鼠中观察到 Co-PCB 接触对血浆中补体成分（C3 和 C4）的影响。当从Co-PCBs对活体的影响方面作为终点来考虑对生殖和发育的毒性时，估计无活性量为1μg/kg。 (4)还发现胎生期暴露和新生儿乳汁暴露影响肝脏中CYP1A1、CYP1A2和CYP2B1/2 mRNA的表达以及血浆中补体系统蛋白的动态变化。

项目成果

Hiroshi Yoshikawa, Mitsuyuki Shirai, Fumiaki Akahori: "Electron paramagnetic resonance analysis of liver and serum in Sprague-Dawley rats exposed subchronically to coplanar pentachlorobiphenyl-congener 3,3',4,4',5"Animal Science Journal. 73. 269-277 (2002

Hiroshi Yoshikawa、Mitsuyuki Shirai、Fumiaki Akahori：“亚慢性暴露于共面五氯联苯同系物 3,3,4,4,5 的 Sprague-Dawley 大鼠肝脏和血清的电子顺磁共振分析”《动物科学杂志》。

Shirota M., Kitazawa I., Inoue K., Doyama A., Muaki M., Haishima A., Yamamoto K., Katoh C., Soda S., Kawabata A., Akahori F., and Shirota K.: "Adverse effects of in utero and lactational exposure to 3, 3', 4, 4', 5-pentachlorobiphenyl (PCB126) on the firs

Shirota M.、Kitazawa I.、Inoue K.、Doyama A.、Muaki M.、Haishima A.、Yamamoto K.、Katoh C.、Soda S.、Kawabata A.、Akahori F. 和 Shirota K.：“

Issei Chiba, Fumiaki Akahori, Shoichi Fujita: "Negative correlation between plasma thyroid hormone levels and chlorinated hydrocarbon levels accumulated in seals from the coast of Hokkaido, Japan"Environmental Toxicology and Chemistry. 20. 1092-1097 (2001

Issei Chiba、Fumiaki Akahori、Shoichi Fujita：“血浆甲状腺激素水平与日本北海道海岸海豹体内积累的氯化烃水平之间的负相关”环境毒理学和化学。

M.Shirota, K.Taya, K.Shirota: "Effects of reduction of the number of primordial follicles on follicular development to achieve puberty in female rats"Reproduciton. 125. 85-94 (2003)

M.Shirota、K.Taya、K.Shirota：“原始卵泡数量减少对雌性大鼠青春期卵泡发育的影响”再现。

Kentaro Q Sakamoto., Tatsuya Kunisue., Mafumi Watanabe., Yasushi Masuda., Hisato Iwata., Shinsuke Tanabe., Fumiaki Akahori., Mayumi Ishizuka., Akio Kazusaka., and Shoichi Fujita.: "Accumulation patterns of polychlorinated biphenyl congeners and origanochl

Kentaro Q Sakamoto.，Tatsuya Kunisue.，Mafumi Watanabe.，Yasushi Masuda.，Hisato Iwata.，Shinsuke Tanabe.，Fumiaki Akahori.，Mayumi Ishizuka.，Akio Kazusaka.，和 Shoichi Fujita.：“多氯联苯同系物和