Elucidation of the epigenetic mechanism of carcinogenesis in pups exposed to chemicals during pregnancy

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09162
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hygiene and public health
• Research Institution: Osaka City University
• Principal Investigator: Wanibuchi Hideki 大阪市立大学, 大学院医学研究科, 教授 (90220970)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: ヒ素 / DMA / 経胎盤ばく露 / 経世代影響 / 発がん / エピジェネティクス

Outline of Final Research Achievements

The concept of developmental origins of health and disease” (DOHaD) has been proposed to link lifestyle-related diseases with the environmental conditions of the early life including the fetal period. Carcinogenic risk though gestational exposure is becoming an important theme for environmental carcinogenesis. Recently, we reported that gestational (transplacental) exposure to organic arsenical dimethylarsinic acid (DMA) enhanced lung and liver carcinogenesis in mice. In the present study, we demonstrated that transplacental exposure to DMA enhanced lung carcinogenesis via histone modification in mice. This finding indicated that the epigenetic alterations induced by arsenicals during the fetal period attribute to the increased risk of cancers in offspring and might serve as useful markers for risk assessment.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

妊娠期における子の発達環境が成人後の疾患リスクに影響を与えるという概念であるDOHaD（Developmental Origins of Health and Disease）説が注目されており、これまでに発達期の低栄養環境による生活習慣病等のリスクを増加させることが報告されている。近年、がんにおいても妊娠期における環境が、将来の発がんリスクに影響を与えることが報告されており、発がんリスクを減少させるため発がん機序の解明が望まれる。我々の研究により明らかとなった有機ヒ素化合物DMAの経胎盤曝露によって生じたエピジェネティック異常が、妊娠期曝露による発がんの機序解明に寄与すると期待される。