Takahashi Osamu, Oishi Shinshi, Yoneyama Masako, Ogata Akio, Kamimura Hisashi
Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health, 24-1 Hyakunincho 3-chome, Shinjuku-ku, Tokyo, 169-0073, Japan.
Arch Toxicol. 2007 Jul;81(7):505-17. doi: 10.1007/s00204-007-0179-4. Epub 2007 Feb 16.
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.
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。