Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Arsenic is a naturally occurring semi-metal and is widely distributed throughout the environment in the air, water, and land. It is well known that the toxicities of arsenic depend on its chemical form. Inorganic arsenic is classified as a human carcinogen (Group 1) by the International Agency for Research on Cancer (IARC). Increased risk of cancers due to chronic exposure to arsenic is a worldwide health problem. Inorganic arsenic is metabolized into organic arsenicals via stepwise reduction and oxidative methylation reactions. We have demonstrated that dimethylarsinic acid (DMA), a major arsenic urinary metabolite, is a complete urinary bladder carcinogen in rats and promotes carcinogenesis in various organs using animal models. We also showed that oxidative DNA damage and increased cell proliferation are involved in the mechanism of carcinogenesis. Based on these findings, IARC concluded that there was sufficient evidence in experimental animals for the carcinogenicity of DMA in 2004.
Recently, we have been studying on effects of fetal exposure to arsenic on the next generation. We showed that transplacental exposure of DMA increased lung and liver cancers in male offspring of mice and transplacental exposure of organic arsenical diphenylarsinic acid (DPAA) increased liver cancers in male offspring of mice. We also revealed that epigenetic abnormalities such as DNA methylation and histone modifications are involved in the carcinogenic mechanism of these organic arsenicals during fetal life and suggested that carcinogenic mechanisms differ between fetal and adult stages of life. It is known that various epigenetic abnormalities accumulate in cancer cells in addition to genetic abnormalities, and epigenetic abnormalities have significant impacts on the cancer development from the early stage of development to progression. The results of our studies indicated that exposure to chemical substances in early stage of development induce epigenetic abnormalities and contributes to carcinogenesis after maturation.
In this symposium, I will summarize our findings on the carcinogenicity of arsenic in experimental animal and its mechanism, especially the carcinogenic effects of fetal exposure.
