Aromatic amine induced urinary bladder carcinogenesis and its abnormal gene expression
| Project/Area Number |
20K10431
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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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| Review Section |
Basic Section 58020:Hygiene and public health-related: including laboratory approach
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| Research Institution | Osaka Metropolitan University (2022)
Osaka City University (2020-2021) |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 芳香族アミン / 職業性膀胱癌 / 遺伝子発現異常 / 膀胱癌治療戦略 |
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| Outline of Research at the Start |
芳香族アミンによる膀胱発がんは以前より知られているが、その詳細な発生メカニズムについては未だ十分には明らかになっていない。
本研究では、芳香族アミン類誘発ラット膀胱上皮の共通した遺伝子発現異常を解析し、膀胱癌発生に至る細胞増殖カスケードに係る機序を解明するとともに、芳香族アミン曝露による職業性膀胱癌を発症した従業員の膀胱癌の次世代シークエンサーを用いた全ゲノム解析を行い、一般の膀胱癌の全ゲノム解析との比較からその発生メカニズムを詳細に検討するとともに治療戦略を立てる。
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| Outline of Final Research Achievements |
Our studies demonstrated that acetoaceto-o-toluidide, aceto-o-toluidide, and o-toluidine can induce proliferative lesions in the bladders of male F344 rats. Analysis of genes exhibiting common aberrant expression in the bladder following the administration of these aromatic amines revealed that these genes predominantly are cancer-related genes, including genes that contribute to TP53 instability. Additionally, we detected higher mutation frequencies of the TP53 gene in occupational bladder cancers compared to sporadic bladder cancers, underlining the pivotal role of TP53 mutation in occupational bladder cancers. Notably, we observed a higher number of gene mutations per case in both types of bladder cancers, suggesting that exposure to aromatic amines may induce distinct mutation patterns. Our findings provides novel insights into the mechanisms of occupational bladder cancers, thereby will promote the development of therapeutic strategies.
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| Academic Significance and Societal Importance of the Research Achievements |
芳香族アミン曝露により発生した職業性膀胱癌において、一般の非喫煙者由来の膀胱癌よりもTP53遺伝子の変異割合が高い傾向を示し、芳香族アミンによる特異的な変異が存在する可能性とともに、癌抑制遺伝子TP53の変異を介した発がん機序が重要であることが示唆された。また、動物実験を介したOTD関連芳香族アミンによる膀胱発癌機序が、職業性膀胱発癌機序解明及び治療戦略の開発に役立つ可能性を示した。
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Report
(4 results)
Research Products
(63 results)
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[Journal Article] The carbonic anhydrase inhibitor acetazolamide inhibits urinary bladder cancers via suppression of β-catenin signaling.2022
Author(s)
Matsue T, Gi M, Shiota M, Tachibana H, Suzuki S, Fujioka M, Kakehashi A, Yamamoto T, Kato M, Uchida J, Wanibuchi H.
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Journal Title
Cancer Sci.
Volume: 113
Issue: 8
Pages: 2642-2653
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Response biomarkers of inhalation exposure to cigarette smoke in the mouse lung2022
Author(s)
Suzuki S, Asai K, Gi M, Kojima K, Kakehashi A, Oishi Y, Matsue T, Yukimatsu N, Hirata K, Kawaguchi T, Wanibuchi H.
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Journal Title
Journal of Toxicologic Pathology
Volume: 35
Issue: 3
Pages: 247-254
DOI
ISSN
0914-9198, 1881-915X
Related Report
Peer Reviewed / Open Access
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[Journal Article] Cell proliferation of rat bladder urothelium induced by nicotine is suppressed by the NADPH oxidase inhibitor, apocynin2021
Author(s)
Suzuki S, Cohen SM, Arnold LL, Pennington KL, Gi M, Kato H, Naiki T, Naiki-Ito A, Wanibuchi H, Takahashi S.
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Journal Title
Toxicology Letters
Volume: 336
Pages: 32-38
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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