Elucidation of the epigenetic mechanism of carcinogenesis in pups exposed to chemicals during pregnancy
| Project/Area Number |
17K09162
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hygiene and public health
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| Research Institution | Osaka City University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| 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 / Dimethylarsinic acid / 胎児期ばく露 / 質量イメージング |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(73 results)
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[Journal Article] Dimethylarsinic acid (DMA) enhanced lung carcinogenesis via histone H3K9 modification in a transplacental mouse model2020
Author(s)
Fujioka, M., Suzuki, S., Gi, M., Kakehashi, A., Oishi, Y., Okuno, T., Yukimatsu, N., Wanibuchi, H.
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Journal Title
Arch Toxicol
Volume: 94
Issue: 3
Pages: 927-937
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Promotion effects of acetoaceto-o-toluidide on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats2019
Author(s)
Yukimatsu, N., Gi, M., Okuno, T., Fujioka, M., Suzuki, S., Kakehashi, A., Yanagiba, Y., Suda, M., Koda, S., Nakatani, T., Wanibuchi, H
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Journal Title
Arch Toxicol
Volume: 93
Issue: 12
Pages: 3617-3631
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] mTOR activation in liver tumors is associated with metabolic syndrome and non-alcoholic steatohepatitis in both mouse models and humans2018
Author(s)
Okuno, T., Kakehashi, A., Ishii, N., Fujioka, M., Gi, M., and Wanibuchi, H.
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Journal Title
Cancers (Basel)
Volume: 10
Issue: 12
Pages: 465-465
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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