研究業績

The possibility that a wide variety of polychlorinated biphenyls (PCBs) and their derivatives are present in the environment necessitates detailed evaluation of their toxicities. A number of PCBs and monohydroxylated PCBs (OH-PCBs) have been reported to have affinities for several nuclear receptors, and some of these compounds have been shown to have harmful effects in animals. In this study, we focused on the retinoid X receptor (RXR) and the retinoic acid receptor (RAR), which play critical roles in development and homeostasis. Specifically, we measured the agonistic activities of 91 OH-PCBs on these receptors by using yeast cells transfected with human RXRβ or RARγ. Of the tested OH-PCBs, 20 exhibited agonistic activity on RXRβ and 35 on RARγ, although their activities were lower than those of the respective endogenous ligands. Most of the OH-PCBs that showed potent activity on RXRβ were tri- or tetrachlorinated compounds, whereas most of the active compounds on RARγ were di-, tri-, or tetrachlorinated compounds. The optimal position for the hydroxyl group relative to the bond linking the aromatic rings was ortho for RXRβ and meta for RARγ. The activities of the OH-PCBs on RXRβ depended strongly on the position of the hydroxyl group, whereas those on RARγ did not. Taken together with the results of our previous studies of compounds with effects on other nuclear receptors, these results provide critical information for further research on receptor-mediated toxicity, endocrine-disrupting effects, and structure-activity relationships.