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雌激素类霉菌毒素玉米赤霉烯酮对SKN、HHUA和HepG2人癌细胞系的激动和拮抗作用。

Agonistic and antagonistic effects of zearalenone, an etrogenic mycotoxin, on SKN, HHUA, and HepG2 human cancer cell lines.

作者信息

Withanage G S, Murata H, Koyama T, Ishiwata I

机构信息

Feed Safety Research Division, National Institute of Animal Health, Tsukuba, Ibaraki, Japan.

出版信息

Vet Hum Toxicol. 2001 Feb;43(1):6-10.

PMID:11205083
Abstract

Zearalenone (ZEA) is a nonsteroidal estrogenic compound mainly produced by the molds Fusarium graminearium and Fusarium culmorum found in a variety of host plants and soil debris around the world. ZEA is usualy non-lethal to animals but is important to livestock producers because its hyperestrogenic effects adversely influence the reproductive performance of animals. There have been suggestions of possible involvement of ZEA in the progression of breast malignancies and tumors of the female reproductive tract in humans. The toxic or stimulatory effects of ZEA and its metabolites alpha-zearalenol and 17-beta-estradiol on SKN, HHUAand HepG2 cells were studied using rapid colorimetric MTT assay. In general, both concentrations of 17-beta-estradiol (100M and 10 nM) were toxic to SKN and HHUA cell cultures. Both ZEA and alpha-zearalenol stimulated the proliferation of SKN and HHUA cells. On HepG2 cells, lower concentrations (10 nM) of 17-beta-estradiol and higher concentrations (100 microM) of ZEA exhibited toxic effects, whereas treatment with higher concentrations of 17-beta-estradiol and lower concentration of ZEA did not show toxic effects. A dose dependent antagonistic effect was observed when the cell cultures were pre-incubated with ICI 182,780, a synthetic estrogen receptor blocker, before estradiol or mycotoxin treatments.

摘要

玉米赤霉烯酮(ZEA)是一种非甾体雌激素化合物,主要由禾谷镰刀菌和黄色镰刀菌产生,这些霉菌在世界各地的多种寄主植物和土壤残渣中均有发现。ZEA通常对动物无致死性,但对家畜生产者而言很重要,因为其高雌激素效应会对动物的生殖性能产生不利影响。有人提出ZEA可能与人类乳腺恶性肿瘤及女性生殖道肿瘤的进展有关。使用快速比色MTT法研究了ZEA及其代谢产物α-玉米赤霉醇和17-β-雌二醇对SKN、HHUA和HepG2细胞的毒性或刺激作用。一般来说,两种浓度的17-β-雌二醇(100μM和10 nM)对SKN和HHUA细胞培养物均有毒性。ZEA和α-玉米赤霉醇均刺激了SKN和HHUA细胞的增殖。对于HepG2细胞,较低浓度(10 nM)的17-β-雌二醇和较高浓度(100μM)的ZEA表现出毒性作用,而用较高浓度的17-β-雌二醇和较低浓度的ZEA处理则未显示出毒性作用。当细胞培养物在雌二醇或霉菌毒素处理前用合成雌激素受体阻滞剂ICI 182,780预孵育时,观察到剂量依赖性拮抗作用。

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