Kanemi Yuso and Transgenerational Epigenetic Inheritance
Tohru Shibuya1, Kennichi Miyakawa2, Yukiharu Horiya1, and Tadasu Fujino3
1 Laboratory of Environmental Epigenetics, Japan
2 Yokohama Dental Clinic
3 Kikuyo Hospital
epilabo@leeg.jp
“Kanemi Yusho (Yusho)” was caused by the contamination of heated PCBs for deodorization during the manufacturing process of rice bran oil at Kanemi Warehouse Co. Ltd., (Kitakyusyu, Fukuoka, Japan) in 1968. People who ingested contaminated rice bran oil developed skin conditions, such as chloracne, as well as liver and kidney diseases. A total of 15,000 people were affected, and it was concluded that the causative agent of “Yusho” was mainly polychlorinated dibenzofurans (PCDFs) derived from heated PCBs. These toxicities were induced by activation of aryl hydroycarbon receptor (AhR).
Research has been conducted by the Department of Dermatology,
Kyushu University, on the treatment of “Yusho” and its causative agent. However, in recent years, an extremely serious problem of inter/trans generational transmission of “Yusho” has arisen in subsequent generations in which similar symptoms were observed. In 2021, research group conducted a survey on the subsequent generations in which similar symptom were observed. In 2021,on volunteer patients and an interim reports was published in June,2022. Approximately 400 patients were surveyed in the next generation, including 66 patients in the third generation. Based on the patients’ chief complaints, the same symptoms as those reported in the originally affected patients were observed at a relatively high frequency. This cannot be explained solely by transplacental or breast milk toxicity, which differs from the direct effects of PCDFs.
Recently, the term “epigenetics” has become increasingly popular in medicine and biology. The term “environmental epigenetics” refers to the disruption of epigenetics due to various environmental factors. Somatic and germ cells are affected by environmental epigenetics. Since 2005, studies of environmental epigenetics in germ cells have mainly been conducted by Skinner’s group, who proved the potency of chemicals in inducing transgenerational epigenetic inheritance (TEI) in rodent experiments. Many other researchers have shown that most endocrine disrupting chemicals (EDCs) possess the capacity to induce TEI. If TEI can explain the transgenerational effects of “Yusho” , detailed data on the TEL in humans caused by a specific chemical substances can be obtained, Notably, TEI in humans, unlike genetic diseases caused by mutations, are likely to pass indefinitely.
If pedigree analysis confirms that the generational problems of “Yusho” originated from TEI, it would be useful to examine blood and cell samples from patients and their descendants on the point of epigenetics. An important genomic region that requires research is imprinting gene, IGF2/H19. Several studies have investigated the relationship among EDCs, AhR, and imprinting gene IGF2/H19.
The general public and surrounding environments are already contaminated by these EDCs, even at low concentrations, and these effects may intensify with time. The possibility that TEIs harm future generations of the general public cannot be ignored. Toxicologicsts must determine the risk of EDCs to future human generations using appropriate statistical assessment models.