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INCREASED INCIDENCE OF BLADDER CANCER IN PEOPLE LIVING IN RADIOCONTAMINATED AREA OF UKRAINE AFTER THE CHERNOBYL DISASTER

Research Project

Project/Area Number 12576005
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Experimental pathology
Research InstitutionOSAKA CITY UNIVERSITY

Principal Investigator

FUKUSHIMA Shoji  OSAKA CITY UNIVERSITY MEDICAL SCHOOL, DEPT.PATHOLOGY, PREFESSOR, 大学院・医学研究科, 教授 (00137077)

Co-Investigator(Kenkyū-buntansha) MORIMURA Keiichirou  OSAKA CITY UNIVERSITY MEDICAL SCHOOL, DEPT.PATHOLOGY, ASSISTANT PROFESSOR, 大学院・医学研究科, 講師 (30315999)
WANIBUCHI Hideki  OSAKA CITY UNIVERSITY MEDICAL SCHOOL, DEPT.PATHOLOGY, ASSOCIATE PROFESSOR, 大学院・医学研究科, 助教授 (90220970)
ALINA M Romanenko  INSTITUTE OF UROLOGY AND NEPHROLOGY ACADEMY OF MEDICAL SCIENCE OF UKRAINE, DEPT.PATHOLOGY, PROFESSOR AND DIRECTRATE
Project Period (FY) 2000 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2003: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2002: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2000: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsChernobyl accident / Bladder cancer / Chernobyl cystitis / Persistent low level exposure of radiation / Oxidative stress damage / Cancer related gene / p53 gene / Growth Factor Receptor / チェルノブイリ原子力発電所 / Growth Factor receptors / Fibroblast Growth Factor Receptor / Epidermal Growth Factor Receptor / 慢性増殖性膀胱炎 / 膀胱がん / 低用量放射線汚染 / チェルノブイリ原子力発電所事故 / 慢性膀胱炎 / 酸化的ストレス障害 / p38 / p50 / p65 / 8-OHdG / iNOS / COX-2 / セシウム137 / サイクリンD1遺伝子
Research Abstract

After the Chernobyl accident, the incidence of urinary bladder cancers in Ukrainian is reported to increase 1.6 times within 15 years. Low level but persistent contamination of radioactive ^<137> Cs in the soil may be one of the main reasons for this increasing bladder cancer incidence. In this research project, we found out the increased incidence of dysplasia and/or bladder cancer including carcinoma in situ, was accompanied with increased ^<137> Cs level in urine among the people living in the radio-contaminated area, who showed no clinical symptoms of bladder cancer. Also we detected that a very specific chronic proliferative atypical cystitis with displastic lesions and/or carcinoma in situ was ubiquitously seen in the inhabitant of this radio-contaninated area. We defined this lesion as "Chernobyl cystitis". In this bladder lesion, several cancer related genes such as p53, p21 and Cyclin D1, were aberrantly expressed and iNOS and COX2 were over-expressed. These results point out … More to the great contribution of oxidative stress to the occurrence of cancer prone bladder lesions seen in this area. Moreover, we detected the difference in the incidences of p53 gene mutations in bladder cancers before and after Chernobyl accident, to be the possible distinct molecular carcinogenic pathway of bladder cancer formation in this area. To further investigate the mechanism underlying bladder carcinogenesis with this specific etiology, we investigated the expression level of growth factor receptor immunohistochemically. High expressions of FGF-R3, EGE-R1 and EGF-R2 were detected in bladder epithelia of radio-contaminated area, compared with those in clean area, and these growth factor receptors were suggested to play an important role in the bladder carcinogenesis after in the Chernobyl accident. From the sequence of the studies in this project, we demonstrated that people living in this radio-contaminated area were in peril of bladder cancer, and that a distinct molecular pathway might exist in the genesis of bladder cancer, based on this specific etiology. Less

Report

(5 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (51 results)

All Other

All Publications (51 results)

  • [Publications] Romanenko, A., Fukushima, S.et al.: "Increased oxidative stress with gene alteration in urinary bladder urothelium after the chernobyl accident."International Journal of Cancer. 86. 790-798 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamamoto S., Fukushima S.et al.: "p53 status in multiple human urothelial cancers : assessment for clonality by the yeast p53 functional assay in combination with p53 immunohistochemistry."Japanese Journal of Cancer Research. 91. 181-189 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima, S., Wanibuchi, H.: "Prevention of urinary bladder cancer : The interface between experimental and human studies."Asian Pacific Journal of Cancer Prevention. 1. 15-33 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima S.: "Possible involvement of O^6-methylguanine formation and p53 dysfunction in mouse urinary bladder carcinogenesis."Mutation Research. 477. 125-130 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Romanenko, A., Fukushima, S.et al.: "Correspondence re : W.Paile's Letter to the editor."Cancer Research. 61. 6964-6965 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Romanenko, A., Fukushima, S.et al.: "DNA damage repair in bladder urothelium after the chernobyl accident in ukraine."The Journal of Urology. 168. 973-977 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima, S.et al.: "Lack of a dose-response relationship for carcinogenicity in the rat liver with low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or N-nitrosodiethylamine."Japanese Journal of Cancer Research. 93. 1076-1082 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Wanibuchi H., Fukushima S.et al.: "Lack of Inhibitory effects of an anti-angiogenesis drug, TNP-470, on rat urinary bladder papillomatosis induced by mechanical stimulation."Journal of Toxicologic Pathology. 15. 197-201 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima, S.et al.: "Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline."Cancer letters. 191. 35-40 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima, S.et al.: "Appropriate models and an understanding of carcinogenic mechanisms -requirements for hazard risk assessment."Asian Pacific Journal of Cancer Prevention. 4. 75-78 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Romanenko, A., Fukushima, S.et al.: "Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation."Cancer Science. 94. 328-333 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima, S.et al.: "Theresholds for carcinogenicity of environmental carcinogens."Journal of Toxicologic Science. 28. 241-241 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morimura K., Fukushima S.et al.: "Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster."Oncology Reports. 11. 881-886 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima S, et al.: "Surgical pathology update 2001, 18th European congress of pathology"ABW Wissenschaftsverlag, Berlin, Genmany. 4 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Cohen, S.M., Fukushima, S.et al.: "Handbook of Toxicologic Pathology. Second Edition."Academic press. 26 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Vozianov, A.F., Romanenko, A., Fukushima, S.: "Health Effects of Chornobyl Accident."DIA Ltd.. 22 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima S., et al.: "Lack of initiation activity in rat liver of low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline"Cancer letters. 191. 35-40 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima S., et al.: "Appropriate models and an understanding of carcinogenic mechanisms -requirements for hazard risk assessment"Asian Pacific Journal of Cancer Prevention. 4. 75-78 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Romanenko, A., Fukushima, S., et al.: "Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation"Cancer Science. 94. 328-333 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Fukushima S., et al.: "Theresholds for carcinogenicity of environmental carcinogens"Journal of Toxicologic Science. 28. 241-241 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morimura K., Fukushima S., et al.: "Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after the Chernobyl disaster"Oncology Reports. 11. 881-886 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Cohen, S.M., Fukushima, S., et al.: "Handbook of Toxicologic Pathology. Second Edition"Academic press. 26 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Vozianov, A.F., Romanenko, A., Fukushima, S: "Health Effects of Chornobyl Accident"DIA Ltd.. 22 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morimmura, K. et al.: "Possible distinct molecular carcinogenic pathways for bladder cancer in Ukraine, before and after Chernobyl disaster"Oncology Reports. 11. 881-886 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Wanibuchi, H. et al.: "Significace of overexpression of metallothionein in mouse urinary bladder focalesions induced by treatment with N-butyl-N-(4-hydroxyburyl)-nitrosamine"Cancer Science. 94. 1052-1058 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukushima, S. et al.: "Liver tumorigenicity of trimethylarsine oxide in male Fischer 344 rats-association with oxidative DNA damage and enhanced cell proliferation"Carcinogenesis. 24. 1827-1835 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukushima, S. et al.: "Theresholds for carcinogenicity of environmental carcinogens"Journal of Toxicological Science. 28. 241 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Romanenko, A. et al.: "Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation"Cancer Science. 94. 328-333 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Romanenko, A. et al.: "DNA damage repair in bladder urothelium after the chernobyl accident in ukraine"The Journal of Urology. 168. 973-977 (2002)

    • Related Report
      2003 Annual Research Report
  • [Publications] Romanenko, A. et al.: "Health Effects of Chernobyl Accident"DIA Ltd., Kiev. 512 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Romanenko, A., Fukushima, S., et al.: "Increased oxidative stress with gene alteration in urinary bladder urothelium after the chernobyl accident"Int.J.Cancer. 86. 790-798 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukushima, S.: "Possible involvement of O^6-methylguanine formation and p53 dysfunction in mouse urinary bladder carcinogenesis"Mut.Res.. 477. 125-130 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kinoshita, A., Fukushima, S., et al.: "Formation of 8-tydroxydeoxyguanosine and cell-cycle arrest in the rat liver via generation of oxidative stress by phenobarbital : association with expression profiles of p21^<WAF1/Cipl>, cyclin D1 and Oggl."Carcinog.. 23. 341-349 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Wei, M., Fukushima, S., et al.: "Carcinogenicity of dimethylarsinic acid in male F344 rats and genetic alterations in induced urinary bladder tumors"Carcinog.. 23. 1387-1397 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Romanenko, A., Fukushima, S., et al.: "DNA damage repair in bladder urothelium after the chernobyl accident in ukraine"J.Urol.. 168. 973-977 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Fukushima, S.et al.: "Lack of a dose-response relationship for carcinogenicity in the rat liver with low doses of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline or N-nitrosodiethylamine"Jpn.J.Cancer Res.. 93. 1076-1082 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Cohen, S.M., Fukushima, S., et al.: "Lower Urinary Tract. In : Handbook of Toxicologic Pathology. Second Edition. Vol. 2"Academic Press. 25 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamoto, S., Fukushima, S., et al.: "p53 status in multiple human urothelial cancers : assessment for clonality by the yeast p53 functional assay in combination with p53 immunohistochemistry"Jpn. J. Cancer Res.. 91. 181-189 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Romanenko, A., Fukushima, S., et al.: "Increased oxidative stress with gene alteration in urinary bladder urothelium after the chemobyl accident"Int. J. Cancer. 86. 790-798 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Romanenko, A., Fukushima, S., et al.: "Correspondence re ; W. Paile's Letter to the editor"Cancer Res.. 61. 6964-6965 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukushima S.: "Possible involvement of O^6-methylguanine formation and p53 dysfunction in mouse urinary bladder carcinogenesis"Mut. Res.. 477. 125-130 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Gen, H., Fukushima, S et al.: "p53 and H-ras mutations and microsatellite instability in renal pelvic carcinomas of NON/Shi mice treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine : different genetic alteration from urinary bladder carcinoma"Jpn. J. Cancer Res.. 92. 1278-1283 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukushilna, S., et al.: "Suppression of chemical carcinogenesis by water-soluble organosulfur componds"J. Nutr.. 131. 1049-1053 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Cohen, S.M., Fukushima, S., et al.: "Lower urinary Tract. In : Handbook of Toxicologic Pathology. Second Edition. vol.2"Academic Press. 337-362 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Romanenko,A.: "Urinary bladder lesions after the chernobyl accident : immunohistochemical assessment of p53, proliferating cell nuclear antigen, cyclin D1 and p21^<WAF1/Cip1>."Jpn.J.Cancer Res.. 90. 144-153 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ozaki,K.: "High susceptibility of p53 (+/-) knockout mice in N-butyl-N-(4-hydroxybutyl) nitrosamine urinary bladder carcinogenesis and lack of frequent mutation in residual allele."Cancer Res.. 58. 3806-3811 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto,S.: "Specific p53 gene mutations in urinary bladder epithelium after the Chernobyl accident."Cancer Res.. 59. 3606-3609 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Lee,C.C.R.: "Reduced expression of the CDK inhibitor p27^<kip1> in rat two-stage bladder carcinogenesis and its association with expression profiles of p21^<WAF1/Cip1> and p53."Carcinogenesis. 20. 1697-1708 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takaba,K.: "Significant overexpression of metallothionein and cyclin D1 and apoptosis in the early process of raturinary bladder carcinogenesis induced by treatment with N-butyl-N-(4-hydroxybutyl) nitrosamine or sodium L-ascorbat"Carcinogenesis. 21. 691-700 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Romanenko,A.: "Increased oxidative stress with gene alteration in urinary bladder urothelium after the chernobyl accident."Int.J.Cancer. 86. 790-798 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukushima,S.: "Carcinogenicity"Kitchin,K.T.. 26 (1999)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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