PM10 Mechanisms of Toxic Action
Exhibit Hall
8:00 AM - Monday
(PM171) Competitive Interaction of Polychlorinated Diphenyl Ethers with Human Transthyretin.
Aoyagi, Mitsuhiro1, Kashima, Yuji2, Hasegawa, Jun3, Sakai, Haruya4, Masunaga, Shigeki5, Okabe, Toshiko6, 1 Graduate School of Environment Information & Sciences, Yokohama National University, Yokohama, Kanagawa, Japan2 Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan3 Department of Environmental Conservation, Ehime University, Matsuyama, Ehime, Japan4 Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan5 Graduate School of Environment Information & Sciences, Yokohama National University, Yokohama, Kanagawa, Japan6 Yokohama City University School of Medicine, Yokohama, Kanagawa, Japan
ABSTRACT- It has been suggested that polyhalogenated aromatic hydrocarbons interfere with thyroid function, because they have a similar structure with L-thyroxine (L-T4) and compete the binding site of transthyretin (TTR), one of thyroid hormone transport proteins. In this study, we investigated the possible interaction of several chlorinated diphenyletherers (PCDEs) as well as various halogenated phenols and nitrophenols with L-T4 using in vitro competitive binding assay. From the result of binding assay of each competitor, IC50 (consentration of competitor at half-maximal specific binding) and the relative binding potency (RBP) against (or compared with) L-T4 were calculated. Chloronitrofen (CNP) and nitrofen (NIP) showed little binding affinity with TTR, if any. In contrast, the RBPs of Irgasan DP300, one of hydroxylated PCDE, was about 1/300. In addition, almost all the halogenated phenols tested competitively displaced 125I- L-T4 from TTR with different potency. Especially iodinated and brominated phenols studied here showed high affinity with TTR (RBP of 2,4,6-triiodophenol was 60 times larger than L-T4). Furthermore, nitrophenols showed binding affinity equivalent to respective chlorophenols when nitro group replaced chlorine at the same position. Because few reports are available concerning the concentrations of Irgasan DP300 and phenols in humans to date, further studies are necessary to clarify the risks of exposure to these compounds.
Key words: halogenated phenols, polychlorinated diphenyl ethers , transthyretin, binding assay