Anti-androgenic activity of 3-methyl-4-nitrophenol in diesel exhaust particles
Anti-androgenic activity of 3-methyl-4-nitrophenol in diesel exhaust particles
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DOI：
10.1016/j.ejphar.2006.06.010
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发表时间：
2006-08-14
影响因子：
5
通讯作者：
Taya, Kazuyoshi
中科院分区：
文献类型：
--
作者：
Li, ChunMei;Taneda, Shinji;Taya, Kazuyoshi
在我们对硝基酚类化合物作为柴油机排气颗粒物中血管扩张剂的研究中，我们发现柴油机排气颗粒物中的硝基酚类化合物不仅具有血管扩张活性，而且在体外和体内具有雌激素活性，在体外还具有抗雄激素活性。我们的努力集中在体外和体内抗雄激素活性的3-甲基-4-硝基苯酚（4-硝基-间甲酚; PNMC），已知的杀虫剂杀螟硫磷的降解产物，在柴油机废气颗粒。我们使用体外重组酵母筛选和体内Hershberger试验研究其抗雄激素活性。重组酵母筛选实验表明，PNMC在低浓度下具有抗雄激素活性。此外，去势的28日龄未成熟雄性大鼠，每只大鼠植入含有结晶睾酮的5 mm长的硅橡胶管，并连续5天皮下注射PNMC，剂量从低至0.01和0.1 mg/kg至1 mg/kg，显示精囊、腹侧前列腺和阴茎头的重量显著降低。在0.1 mg/kg PNMC处理组中，血浆促卵泡激素（FSH）和促黄体生成素（LH）水平显著升高。我们的研究结果表明，柴油机排气颗粒中的PNMC显然具有抗雄激素活性，在体外和体内，因此可以被认为是一种内分泌干扰化学品。(c)2006 Elsevier B. V.保留所有权利。
In our continuing studies on nitrophenol derivatives as vasodilators in diesel exhaust particles, we have reported that nitrophenols in diesel exhaust particles possess not only vasodilatory activity but also estrogenic activity in vitro and in vivo, as well as anti-androgenic activity in vitro. Our efforts here were focused on the in vitro and in vivo anti-androgenic activity of 3-methyl-4-nitrophenol (4-nitro-m-cresol; PNMC), known a degradation product of the insecticide fenitrothion, in diesel exhaust particles. We investigated its anti-androgenic activity using an in vitro recombinant yeast screen and in vivo Hershberger assays. Recombinant yeast screen assay showed that PNMC possesses anti-androgenic activity at low concentrations. Furthermore,castrated 28-day-old immature male rats each implanted with a 5-mm-long silastic tube containing crystalline testosterone and injected with PNMC subcutaneously at doses from as low as 0.01 and 0.1 mg/kg up to 1 mg/kg for 5 consecutive days showed significantly decreased weights of the seminal vesicles, ventral prostate, and glans penis. Plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were significantly increased in the 0.1 mg/kg PNMC treatment group. Our results demonstrate that PNMC in diesel exhaust particles clearly has anti-androgenic activity both in vitro and in vivo and can therefore be considered as an endocrine-disrupting chemical. (c) 2006 Elsevier B.V. All rights reserved.