1997 Fiscal Year Annual Research Report

c-Ha-rasトランスジェニックラットの発がん感受性の解析

Research Project

Project/Area Number	09253253
Research Institution	National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
Principal Investigator	鳥山弘靖国立がんセンター, 研究所・化学療法部, 研究員 (70156537)
Co-Investigator(Kenkyū-buntansha)	津田洋幸国立がんセンター, 研究所・化学療法部, 部長 (10163809) 朝元誠人国立がんセンター, 研究所・化学療法部, 室長 (50212494)
Keywords	c-Ha-ras / トランスジェニックラット / 発がん感受性 / 乳腺発がん / 膀胱発がん / MNU / DMBA / BBN
Research Abstract	ヒトのがん組織から高頻度に活性型が検出されるc-Ha-rasがん遺伝子がほぼ全臓器で発現しているプロト型c-Ha-ras遺伝子導入ラットを作成し,以下の臓器における発がん感受性の亢進について確認した。 1.乳腺の発がん感受性 50日齢のc-Ha-ras雌トランスジェニックラットにN-methyl-N-nitrosourea(MNU)50mg/kgを1回静脈内投与したところ,8週間という短期間内に100%の動物に乳腺がんが多発した。対照群のnon-Tgラットでは29.2%であり、有意に乳腺の高発がん感受性を示すことを明らかにした。MNU投与により誘発されたTgラットの乳腺がんにおいて,導入したc-Ha-ras遺伝子ならびに内在性のc-Ha-rasの変異は全く認められなかったが,対照群に発生した乳腺がんでは,内在性のc-Ha-ras遺伝子の変異を比較的高率(28.6%)に認めた。さらに,乳腺に対する発がん物質である7,12-dimethylbenz[a]anthracene(DMBA)40mg/kgの投与によっても,このTgラットは、がんの発生期間,発生頻度ならびに発生個数いずれの項目においても,対照群と比較して高発がん感受性を示すことを明らかにした。 2.膀胱発がん感受性生後6週齢のc-Ha-rasTg雄ラットにN-buthyl-N-(4-hydroxy-bytyl)nitrosoamine(BBN)を0.05%の用量で10週間飲水投与し、全期間20週で屠殺し、膀胱を病理組織学的に検索したところ,ヒトに類似した表在性膀胱がんが発生し、個数において発がん感受性の亢進が認められた。膀胱がんの発生頻度には non-Tgラットと比較して有意な差は認められなかった。TgラットにおけるBBN誘発膀胱がんではごく低頻度に内在性のc-Ha-ras遺伝子にのみ変異が認められた。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Toriyama-Baba,H.et al.: "Triazine derivatives inhibit rat hepatocarcinogenesis but do not enhance gap iunctional intercellular communication." Jpn.J.Cancer Res.88. 12-17 (1997)
[Publications] Toriyama-Baba,H.et al.: "Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats." Jpn.J.Cancer Res.88. 523-526 (1997)
[Publications] Toriyama-Baba,H.et al.: "Chemopreventive potential of α-carotene against mouse liver and lung tumor development:comparison with β-carotene α-tocopherol." Food Factors for Cancer Prevention,Tokyo,Springer-Verlag. 529-532 (1997)
[Publications] Toriyama-Baba,H.et al.: "Inhibition of initiation and early stage development of aberrant crypt foci and enhanced natural killer activity in male rats administered bovine lactoferrin concomitantly with azoxymethane." Cancer Lett.121. 211-216 (1997)
[Publications] Asamoto,M.et al.: "Decreased expression of the p16/MTS1 gene without mutation is frequent in human urinarv bladder carcinomas." Jpn.J.Clin.Oncol.27. 22-25 (1997)
[Publications] Asamoto,M.et al.: "Defferential dose-dependent effects of α-,β-carotenes and lycopene on gap-iunctional intercellular communication in rat liver in vivo." Jpn.J.Cancer Res.88. 1121-1124 (1997)
[Publications] Tsuda,H.et al.: "Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model." Carcinogenesis. 18. 377-381 (1997)
[Publications] Tsuda,H.et al.: "Demonstration of ras and p53 gene mutations in carcinomas in the forestomach and intestine and soft tissue sarcomas induced by N-methyl-N-nitrosourea in the rat." Jpn.J.Cancer Res.88. 129-136 (1997)
[Publications] Tsuda,H.et al.: "Potential preventive effects of chelidonium majis L.(Papaveraceae)herb extract on glandular stomach tumor development in rats treated with N-methyl-N'-nitro-N nitrosoguanidine(MNNG) and hypertonic sodium chlorido." Cancer Lett.112. 203-208 (1997)
[Publications] Tsuda H.et al.: "Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung." Br.J.Cancer. 75(5). 650-655 (1997)
[Publications] Tsuda,H.et al.: "Markedly induced asialoGM1^+ CD8^+T cell production and enhancement of antimetastatic activity by interferon β with folic or folinic acid." Cancer Immunol.Immunother.44. 65-69 (1997)
[Publications] Tsuda,H.et al.: "Somatic mutation of the tuberous sclerosis(Tsc2)tumor suppressor gene in chemically induced rat renal carcinoma cell." J.Urol.158. 275-278 (1997)
[Publications] Tsuda H.et al.: "Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model." Food Factors for Cancer Prevention,Tokyo,Springer-Verlag. 200-203 (1997)
[Publications] Tsuda H.et al.: "Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and-9 activities." Int.J.Cancer. 73. 607-612 (1997)
[Publications] Tsuda H.et al.: "Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN,MNU and DMH." Cancer Lett.120. 15-22 (1997)
[Publications] Tsuda H.et al.: "Carcinogenicity of methylurea or morpholine in combination with sodium nitrite in a rat multi-organ carcinogenesis bioassay" Jpn.J.Cancer Res.88. 797-806 (1997)
[Publications] Toriyama-Baba,H.et al.: "Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1.2-dimethylhydrazine initiation." Carcinogenesis. 19(1). 81-85 (1998)

1997 Fiscal Year Annual Research Report

c-Ha-rasトランスジェニックラットの発がん感受性の解析

Principal Investigator

鳥山 弘靖 国立がんセンター, 研究所・化学療法部, 研究員 (70156537)

Research Products

[Publications] Toriyama-Baba,H.et al.: "Triazine derivatives inhibit rat hepatocarcinogenesis but do not enhance gap iunctional intercellular communication." Jpn.J.Cancer Res.88. 12-17 (1997)

[Publications] Toriyama-Baba,H.et al.: "Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats." Jpn.J.Cancer Res.88. 523-526 (1997)

[Publications] Toriyama-Baba,H.et al.: "Chemopreventive potential of α-carotene against mouse liver and lung tumor development:comparison with β-carotene α-tocopherol." Food Factors for Cancer Prevention,Tokyo,Springer-Verlag. 529-532 (1997)

[Publications] Toriyama-Baba,H.et al.: "Inhibition of initiation and early stage development of aberrant crypt foci and enhanced natural killer activity in male rats administered bovine lactoferrin concomitantly with azoxymethane." Cancer Lett.121. 211-216 (1997)

[Publications] Asamoto,M.et al.: "Decreased expression of the p16/MTS1 gene without mutation is frequent in human urinarv bladder carcinomas." Jpn.J.Clin.Oncol.27. 22-25 (1997)

[Publications] Asamoto,M.et al.: "Defferential dose-dependent effects of α-,β-carotenes and lycopene on gap-iunctional intercellular communication in rat liver in vivo." Jpn.J.Cancer Res.88. 1121-1124 (1997)

[Publications] Tsuda,H.et al.: "Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model." Carcinogenesis. 18. 377-381 (1997)

[Publications] Tsuda,H.et al.: "Demonstration of ras and p53 gene mutations in carcinomas in the forestomach and intestine and soft tissue sarcomas induced by N-methyl-N-nitrosourea in the rat." Jpn.J.Cancer Res.88. 129-136 (1997)

[Publications] Tsuda,H.et al.: "Potential preventive effects of chelidonium majis L.(Papaveraceae)herb extract on glandular stomach tumor development in rats treated with N-methyl-N'-nitro-N nitrosoguanidine(MNNG) and hypertonic sodium chlorido." Cancer Lett.112. 203-208 (1997)

[Publications] Tsuda H.et al.: "Inhibitory effects of docosahexaenoic acid on colon carcinoma 26 metastasis to the lung." Br.J.Cancer. 75(5). 650-655 (1997)

[Publications] Tsuda,H.et al.: "Markedly induced asialoGM1^+ CD8^+T cell production and enhancement of antimetastatic activity by interferon β with folic or folinic acid." Cancer Immunol.Immunother.44. 65-69 (1997)

[Publications] Tsuda,H.et al.: "Somatic mutation of the tuberous sclerosis(Tsc2)tumor suppressor gene in chemically induced rat renal carcinoma cell." J.Urol.158. 275-278 (1997)

[Publications] Tsuda H.et al.: "Enhancement by indole-3-carbinol of liver and thyroid gland neoplastic development in a rat medium-term multiorgan carcinogenesis model." Food Factors for Cancer Prevention,Tokyo,Springer-Verlag. 200-203 (1997)

[Publications] Tsuda H.et al.: "Inhibitory effects of oleic and docosahexaenoic acids on lung metastasis by colon-carcinoma-26 cells are associated with reduced matrix metalloproteinase-2 and-9 activities." Int.J.Cancer. 73. 607-612 (1997)

[Publications] Tsuda H.et al.: "Chemoprevention by lycopene of mouse lung neoplasia after combined initiation treatment with DEN,MNU and DMH." Cancer Lett.120. 15-22 (1997)

[Publications] Tsuda H.et al.: "Carcinogenicity of methylurea or morpholine in combination with sodium nitrite in a rat multi-organ carcinogenesis bioassay" Jpn.J.Cancer Res.88. 797-806 (1997)

[Publications] Toriyama-Baba,H.et al.: "Chemopreventive effects of carotenoids and curcumins on mouse colon carcinogenesis after 1.2-dimethylhydrazine initiation." Carcinogenesis. 19(1). 81-85 (1998)

鳥山弘靖国立がんセンター, 研究所・化学療法部, 研究員 (70156537)