1.Presence of Unknown Substances Which Bind to Various Human Nuclear Receptors in Aquatic Environment: Focusing on Environmental Retinoides
Division of Sustainable Energy and Environmental Engineering, Graduate School of Engineering, Osaka University
For sustainable and safe use of water, it is requisite to fully understand the risks existing in the aquatic environment, i.e. water-derived adverse effects on human health and also on ecosystems. Since cascading and/or repeated use of water should be increased as the countermeasures for the water shortage, understandings of the whole possible risks in water will be more and more important especially in Asia, because water demand shows very sharp increase in this developing region.
Endocrine disrupting chemicals (EDCs), which disrupt or alter the functions of the endocrine system and consequently cause adverse effects in intact organisms, have been recognized as one of the important pollutants in aquatic environment recently. The major mechanism by which EDCs exert their effects is through their direct interaction with nuclear receptors (NRs), and several field surveys have been performed concerning the occurrence of EDCs in aquatic environment including wastewater treatment plants (WWTPs), but most of them focused on EDCs which can bind to steroid hormone receptors like estrogen receptor (ER). Therefore, still very little is known about the EDCs which interact with NRs other than steroid hormone receptors.
Our research group examined the agonistic activity of surface water in Japan on five human NRs (ER, TR; thyroid hormone receptor, RAR; retinoic acid receptor, RXR; retinoid X receptor, VDR; vitamin D receptor) by a yeast two hybrid assay (Nishikawa et al., Toxicol. Appl Pharmacol, 19: 2502-2516, 1999) so as to assess the potential endocrine disruptive effects via a variety of NRs as unknown risks in aquatic environment.
A total of 16 river water samples (100 times concentrated), 8 showed significant agonistic activity to ER. On the other hand, a significant agonistic activity to TR, RAR, RXR, and VDR was shown from 6, 15, 6, and 9 samples, respectively. The relative agonistic activity on RAR were the highest among the five NRs tested. The results suggested that EDs with agonistic activity to various kinds of NRs exist commonly in aquatic environment and especially RAR agonists should be intensively studied due to their frequent detection with relatively high activity. We have to emphasize RAR agonists may cause a severe risk against aquatic ecosystems, because excess retinoid signaling can lead to multiple developmental toxicity in various animals.
Based on the results above, more extensive survey on RAR agonists was performed. Several aquatic samples including samples from WWTPs were additionally examined for their RAR agonistic activity. The research results strongly suggested that the contamination with RAR agonists is ubiquitous in the aquatic environment in Japan, though WWTPs can considerably remove RAR agonistic activity contained in the influent. We have also detected a significant high level of RAR agonistic activity from the effluent of WWTPs of Beijing, China, suggesting RAR agonists exist not only in Japan but also in other countries. The RAR agonists existing in the aquatic environment should be fully identified in future to accurately assess the possible risks and to control the risks.