Latest Findings of Yusho and Its Therapeutic Development

Yusho incident is an unprecedented mass food poisoning that occurred in the western area of Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls (PCBs) and various dioxins and dioxin-like compounds, such as polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). The victims of Yusho have suffered from characteristic skin manifestations in company with systemic, ophthalmological, and mucosal symptoms for a long period. Since the outbreak of Yusho, the Study Group of Yusho has been conducting annual medical check-ups on Yusho victims. We describe here the latest research findings of chronic dioxin-induced toxicity to Yusho patients and the mechanisms of toxicities of dioxins through the aryl hydrocarbon receptor (AhR) pathway. High amounts of PCBs and PCDFs are still present in a number of patients with Yusho. The patients have persistent various symptoms, some of which were significantly associated with blood levels of PCBs, dioxins, or dioxin-like compounds. The adverse effects on the next generation are also found. According to the findings of recent basic studies, the biological and toxicological effects mediated by the AhR system have been becoming clear; therefore, the therapeutic interventions may be found in the near future.