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对二氯苯在未成熟小鼠和大鼠中的抗雌激素作用。

Antiestrogenic effect of paradichlorobenzene in immature mice and rats.

作者信息

Takahashi Osamu, Oishi Shinshi, Yoneyama Masako, Ogata Akio, Kamimura Hisashi

机构信息

Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health, 24-1 Hyakunincho 3-chome, Shinjuku-ku, Tokyo, 169-0073, Japan.

出版信息

Arch Toxicol. 2007 Jul;81(7):505-17. doi: 10.1007/s00204-007-0179-4. Epub 2007 Feb 16.

Abstract

A significant increase/decrease in uterine and ovarian weights was occasionally seen in immature mice and rats subcutaneously administered paradichlorobenzene (PDCB) at doses of 22-67 mg/kg/day, but the results were not necessarily reproducible. PDCB at a dose of 800 mg/kg/day always reduced uterine and ovarian weights. Intraperitoneal PDCB at doses more than 400 mg/kg/day significantly inhibited the uterotrophic effect of beta-estradiol (E2) in CD-1 (ICR) mice. E2-induced uterotrophy was dose-dependently prevented by 204-400 mg PDCB/kg/day in C57BL/6N (Ah responsive) mice but not DBA/2N (Ah non-responsive) mice. While PDCB did not bind to estrogen receptor (ER(alpha)) up to 10(-3) M. Hepatic ethoxyresorufin-O-deethylase in adult female C57BL/6N mice was induced by i.p. administration of PDCB. Induction activity of PDCB may be 10(5)-10(6) times lower than that of 2,3,7,8-tetrachlorodibenzo-p-dioxin. These results suggest that PDCB is a weak antiestrogenic/antiuterotrophic compound possibly due to ER modulation through arylhydrocarbon receptor.

摘要

在以22 - 67毫克/千克/天的剂量皮下给予对二氯苯(PDCB)的未成熟小鼠和大鼠中,偶尔可见子宫和卵巢重量显著增加/减少,但结果不一定可重复。每天800毫克/千克的PDCB剂量总能降低子宫和卵巢重量。在CD - 1(ICR)小鼠中,每天腹腔注射超过400毫克/千克剂量的PDCB可显著抑制β-雌二醇(E2)的子宫营养作用。在C57BL / 6N(Ah反应型)小鼠中,每天204 - 400毫克PDCB /千克可剂量依赖性地抑制E2诱导的子宫肥大,但在DBA / 2N(Ah无反应型)小鼠中则不然。虽然高达10^(-3) M的PDCB不与雌激素受体(ER(α))结合。成年雌性C57BL / 6N小鼠的肝乙氧基异吩唑酮 - O - 脱乙基酶可通过腹腔注射PDCB诱导。PDCB的诱导活性可能比2,3,7,8 - 四氯二苯并 - p - 二恶英低10^5 - 10^6倍。这些结果表明,PDCB可能是一种弱抗雌激素/抗子宫营养化合物,可能是由于通过芳烃受体调节雌激素受体所致。

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