Low-dose signaling toxicity effects of bisphenol compounds on the cooperative action between the nuclear receptors

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12340
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63030:Chemical substance influence on environment-related
• Research Institution: Sojo University
• Principal Investigator: LIU XIAOHUI 崇城大学, 生物生命学部, 准教授 (60596849)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ビスフェノール / 有害化学物質 / 核内受容体 / シグナル毒性 / 転写制御

Outline of Final Research Achievements

The adverse effects of bisphenol A (BPA) on human health have been believed to occur by “the toxicity in signalling through nuclear receptors (NRs).” To avoid such hazardous BPA, various kinds of BPA-free plasticwares made of so-called next-generation bisphenol compounds are increasingly being seen as important, and are increasingly being produced. However, almost none of these bisphenols have been evaluated for their signalling toxicity. In this study, we attempted to elucidate the molecular mechanisms of such low-dose signalling toxicity of bisphenols. As a result, the following four issues were clarified. (i) ERs are strongly activated by BPA when constitutively self-activated NR co-exists. (ii) There are several bisphenols showing a high risk for human health through some certain NRs. (iii) Some bisphenols act as ERα-agonist and also as ERβ-antagonist. (iv) The structural element responsible for the ERβ-antagonist activity was identified to be the London dispersing force.

Free Research Field

化学物質影響化学、受容体科学

Academic Significance and Societal Importance of the Research Achievements

豊かな現代生活を彩る化学製品から漏出する原料ビスフェノールＡ（BPA）。このBPAがもたらす深刻な、メカニズム不明の内分泌撹乱作用。ヒトの健康に悪影響を及ぼすBPAの内分泌撹乱作用は、核内受容体を介したシグナル毒性と考えられている。本研究は、BPAを含む新世代ビスフェノールのこうしたヒト遺伝子に対するシグナル毒性の分子機構を解明しようとするもので、学術的意義、社会的意義はきわめて大きい。また、ヒト核内受容体48種のうち約４分の１存在する自発活性化型核内受容体の、通常の転写因子としての機能とは別な、しかし、本質的に備わった新奇な機能を明らかにする点でもその意義は大きい。