Aromatic amine induced urinary bladder carcinogenesis and its abnormal gene expression

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K10431
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 58020:Hygiene and public health-related: including laboratory approach
• Research Institution: Osaka Metropolitan University (2022); Osaka City University (2020-2021)
• Principal Investigator: Wanibuchi Hideki 大阪公立大学, 大学院医学研究科, 教授 (90220970)
• Project Period (FY): 2020-04-01 – 2023-03-31
• 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

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.

Free Research Field

衛生学および公衆衛生学分野関連:実験系を含む

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。