异丙苯二酮通过雌激素和雄激素受体产生的潜在内分泌干扰效应:利用体外测定和硅学模型进行评估

IF 2.3 3区 农林科学 Q3 FOOD SCIENCE & TECHNOLOGY Applied Biological Chemistry Pub Date : 2024-08-30 DOI:10.1186/s13765-024-00932-4
Ji-Yeon Yang, Jeong-Hyun Lim, Soo-Jin Park, Youmi Jo, Si Young Yang, Min-Kyoung Paik, So-Hye Hong
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引用次数: 0

摘要

本研究采用体外和硅学测试方法,就具有代表性的二氯苯基二甲酰胺类杀菌剂异丙苯啶对内分泌系统的不利影响提供证据。在本研究中,我们采用了 HeLa9903 稳定转染反式激活试验(OECD TG 455)、22Rv1/MMTV_GR-KO 雄激素受体转录激活试验(OECD TG 458)以及 VEGA QSAR 进行毒性预测。结果表明,异丙双酮没有雌激素受体拮抗作用或雄激素受体激动作用;不过,异丙双酮被确定为雌激素受体激动剂(PC10 对数值小于-9)和雄激素受体拮抗剂(IC30 对数值为-4.58),对本研究中使用的人类细胞系没有内在毒性。VEGA QSAR 用于评估五种结构与异丙酮相似的物质。结果发现,其中四种化学物质具有阳性雄激素受体和芳香化酶活性,并具有发育毒性。这些结果表明,异丙二酮调节类固醇激素受体之间的相互作用,是一种潜在的生殖毒性物质。
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Potential endocrine-disrupting effects of iprodione via estrogen and androgen receptors: evaluation using in vitro assay and an in silico model

This study was conducted to provide evidence, using in vitro and in silico testing methods, regarding the adverse effects of iprodione, a representative dichlorophenyl dicarboxamide fungicide, on the endocrine system. In the present study, we used the HeLa9903 stably transfected transactivation assay (OECD TG 455), 22Rv1/MMTV_GR‒KO androgen receptor transcriptional activation assay (OECD TG 458), and toxicity prediction using VEGA QSAR. Our results showed that iprodione had no estrogen receptor antagonistic or androgen receptor agonistic effects; however, iprodione was determined to be an estrogen receptor agonist (log PC10 value is less than − 9) and androgen receptor antagonist (log IC30 value is − 4.58) without intrinsic toxicity against the human cell lines used in this study. VEGA QSAR was used to evaluate five substances with structures similar to that of iprodione. Among them, four chemicals were found to have positive androgen receptor and aromatase activities and have been observed to be developmental toxicants. These results suggest that iprodione regulates steroid hormone receptor interactions and is a potential reproductive toxicant.

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来源期刊
Applied Biological Chemistry
Applied Biological Chemistry Chemistry-Organic Chemistry
CiteScore
5.40
自引率
6.20%
发文量
70
审稿时长
20 weeks
期刊介绍: Applied Biological Chemistry aims to promote the interchange and dissemination of scientific data among researchers in the field of agricultural and biological chemistry. The journal covers biochemistry and molecular biology, medical and biomaterial science, food science, and environmental science as applied to multidisciplinary agriculture.
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