2002 Fiscal Year Final Research Report Summary
Studies on in vivo evaluation system of treatment for cancer prevention and progression using cancer prone gene-engineered mice
| Project/Area Number |
12558097
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Laboratory animal science
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| Research Institution | Central Institute for Experimental Animals |
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Principal Investigator |
OHNISHI Yasuyuki Cent. Inst. Exp. Anim. Lab. Oncology Head, 腫瘍研究室, 室長 (70201382)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAOKI Norikazu Cent. Inst. Exp. Anim. Res. Project Ctr. Vice Director, 副所長 (50055860)
USUI Toshimi Cent. Inst. Exp. Anim. Carcinogenicity Testing Ctr. Head, 医薬品評価センター, センター長 (10311234)
HIOKI Kyoji Cent. Inst. Exp. Anim. Lab. Animal Breeding Head, 飼育技術研究室, 室長 (80208735)
OKADA Masaji Kinki Chuo Hosp. Clinical Res. Ctr. Head, 臨床研究センター, 部長 (40160684)
ARAI Toshiro Nippon Vet. Zootech. Univ. Dept. Biochem. Prof., 獣医生理化学教室, 助教授 (70184257)
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| Project Period (FY) |
2000 – 2002
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| Keywords | H-ras / IL-6 / transgenic / knockout / bigenic / cancer prevention / mouse / urethane |
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| Research Abstract |
We studied to establish in vivo evaluation system of treatment for cancer prevention and progression using cancer prone gene-engineered mice. We have been studying carcinogenicity testing model using rasH2 transgenic mice harboring human prototype H-ras oncogene. In this study, we established urethane-induced lung cancer model with very rapid tumorigenicity. We applied this cancer prone mice system for evaluation of drug or treatment protocol for cancer protection or prevention of cancer progression such as chemoprevention.
The rasH2 mice were injected urethane to induce lung tumor. After or before urethane injection, IL-6 related gene complex (IL-6, IL-6 receptor and gp130) was challenged into the mice. The incidence of lung tumor formation in the urethane injected rasH2 mice was clearly reduced, meaning the IL-6 related gene complex has chemoprevention effects.
The mutational analyses of introducing human H-ras were performed in the lung tumor which induced by urethane and vinylcarbamate (VC, proximal carcinogen of urethane). The results showed almost all tumors had mutation at the 61st codon of H-ras. These results suggested that point mutations at codon 61 of the transgene play an important role in the carcinogenesis of VC- and urethane- induced lung tumors in rasH2 mice.
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