Furuta Chie, Suzuki Akira K, Taneda Shinji, Kamata Kazuyuki, Hayashi Hideyuki, Mori Yoki, Li Chunmei, Watanabe Gen, Taya Kazuyoshi
Laboratory of Veterinary Physiology, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Biol Reprod. 2004 May;70(5):1527-33. doi: 10.1095/biolreprod.103.024810. Epub 2004 Jan 21.
We recently isolated 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC) and 4-nitro-3-phenylphenol (PNMPP) from diesel exhaust particles (DEP) and identified them as vasodilators. Because these compounds are alkylphenolic derivatives that might mimic hormones, we evaluated their estrogenic activity by using recombinant yeast screens, myometrial contractility assays, and in vivo uterotrophic assays. Recombinant yeast screen assays showed that both PNMC and PNMPP possess estrogenic activity. Furthermore, ovariectomized 25-day-old immature female rats injected with PNMC and PNMPP subcutaneously for 2 days showed significant increases in uterine weight among those receiving 100 mg/kg PNMC and 0.1 and 1.0 mg/kg PNMPP. To clarify further the estrogenic activity of PNMC and PNMPP, rat uterine horns were monitored in organ bath chambers for myometrial contractility in response to oxytocin (OT). Significant differences occurred in the initial and maximum contractilities to OT at 0.25 and 25 mIU/ml in uterine horns obtained from animals treated with 100 mg/kg PNMC and in the maximum contractilities to OT at 0.025, 0.25, and 25 mIU/ml in those from rats treated with 0.1 mg/kg PNMPP. These results clearly demonstrated that PNMC and PNMPP in DEP have estrogenic activity both in vitro and in vivo and might therefore be considered as endocrine-disrupting chemicals.
我们最近从柴油尾气颗粒（DEP）中分离出了3-甲基-4-硝基苯酚（4-硝基间甲酚；PNMC）和4-硝基-3-苯基苯酚（PNMPP），并将它们鉴定为血管舒张剂。由于这些化合物是可能模拟激素的烷基酚衍生物，我们通过使用重组酵母筛选、子宫肌层收缩性测定和体内子宫增重测定来评估它们的雌激素活性。重组酵母筛选测定表明，PNMC和PNMPP都具有雌激素活性。此外，对25日龄未成熟雌性大鼠进行卵巢切除，皮下注射PNMC和PNMPP 2天，在接受100 mg/kg PNMC以及0.1和1.0 mg/kg PNMPP的大鼠中，子宫重量显著增加。为了进一步阐明PNMC和PNMPP的雌激素活性，在器官浴槽中监测大鼠子宫角对催产素（OT）的子宫肌层收缩性。在用100 mg/kg PNMC处理的动物所获得的子宫角中，对0.25和25 mIU/ml OT的初始和最大收缩性存在显著差异；在用0.1 mg/kg PNMPP处理的大鼠所获得的子宫角中，对0.025、0.25和25 mIU/ml OT的最大收缩性存在显著差异。这些结果清楚地表明，DEP中的PNMC和PNMPP在体外和体内均具有雌激素活性，因此可能被视为内分泌干扰化学物质。
