1998 年度実績報告書

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

研究課題

研究課題/領域番号	10151258
研究機関	国立がんセンター
研究代表者	鳥山弘靖国立がんセンター, 化学療法部, 研究員 (70156537)
研究分担者	津田洋幸国立がんセンター, 化学療法部, 部長 (10163809) 落谷孝広国立がんセンター, 分子腫瘍学部, 室長 (60192530) 朝元誠人国立がんセンター, 化学療法部, 室長 (50212494)
キーワード	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 / 導入遺伝子変異 / 食道発がん / MNU / NMBA
研究概要	発がん機構の解析や発がん物質の効率的な検索を可能にする発がん高感受性動物の作出を目的にヒトプロト型c-Ha-rasトランスジェニック(Tg)ラットを作出した。このTgラットはMNUおよびDMBAにより乳腺発がん高感受性形質を示した。MNU投与後8週の雌Tgラットに発生した乳腺腫瘍組織の導入遺伝子変異についてclevge resistant bandをRFLPにて解析したところ, codon12に86.8%の頻度で変異が見い出され,codon61には変異の無いことが分かった。また,DMBA投予後16週の乳腺がんでは,codon12に25%の頻度で変異が,codon61では35%に変異の有ることが分かった。しかし,一腫瘍DNAのサブクローニング法とRFLPによる変異シグナルの強度の解析により,がん組織中の変異を持つ細胞の割合は少ないことを明らかにした。さらに,乳腺を標的とする食品中の発がん物質であるPhIPの投与では,投予後8週のTgラットのすべてに乳腺がんの発生が認められたが,野生型ラットには全く認められなかった。発生した乳腺がん組織における導入遺伝子では,codon12に385%で,codon61では23.1%に変異があった。しかし変異を持つ細胞の割合はMNU投与の場合と同様に少なかった。従って,乳腺発がん高感受性形質には導入遺伝子の変異以外に別の機序が関与していることが示唆された。 TgラットにNMBAを投与したところ,顕著な食道腫瘍の増加が認められ,食道においても発がん高感受性形質であることも明らかとなった。食道腫瘍における遺伝子変異を検索した結果,導入遺伝子のcodon12の76%に変異があったが,codon61には変異の無いことが明らかとなった。また,食道腫瘍では変異を持つ細胞の割合が多いことが明らかになった。

研究成果

(29件)

すべてその他

すべて文献書誌 (29件)

[文献書誌] 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)
[文献書誌] Toriyama-Baba,H.et al.: "Enhanced tumorigenicity of rat bladder squamous cell carcinoma cells after abrogation of gap junctional intercellular communication." Jpn.J.Cancer Res.89. 481-486 (1998)
[文献書誌] Toriyama-Baba,H.et al.: "p16 gene overexpression in mouse bladder carcinomas." Cancer Lett.127. 9-13 (1998)
[文献書誌] Toriyama-Baba,H.et al.: "Molecular cloning and function analysis of cDNA encoding a rat leukemia inhibitory factor: towards generation of pluripotent rat embryonic stem cells." Oncogene. 16. 3189-3196 (1998)
[文献書誌] Tsuda,H.et al.: "Implications of the hyperinsulinaemia-diabetes-cancer link for preventive efforts." Eur.J.Cancer Prev.7. 89-107 (1998)
[文献書誌] Tsuda,H.et al.: "Soluble and insoluble fiber influences on cancer development." Oncology Hematology. 27. 229-242 (1998)
[文献書誌] Tsuda,H.et al.: "Physical exercise:a pillar for cancer prevention?" Eur.J.Cancer Prev.7. 177-193 (1998)
[文献書誌] Tsuda,H.et al.: "Orthotopic growth and metastasis of human non-small cell lung carcinoma cells injected into pleural cavity of nude mice." Cancer Lett.127. 203-209 (1998)
[文献書誌] Tsuda,H.et al.: "Cross-country comparisons provide evidence of a strong link between female lung and colon adenocarcinoma development." The Cancer Journal. 11(5). 259-262 (1998)
[文献書誌] Tsuda,H.et al.: "Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats." Adv.Exp.Med.Biol.443. 273-284 (1998)
[文献書誌] Tsuda,H.et al.: "Histogenetic stereological reconstruction of rat basophilic,Clear and oncocytic neoplastic renal cell lesions using carbonic anhydrase type II-PAS double-stained sections." Toxicol.Pathol.26(6). 769-776 (1998)
[文献書誌] Tsuda,H.et al.: "Modulation of dihydroxy-di-n-propylnitrosamine-induced liver lesion development in opisthorchis-infected syrian hamsters by praziquantel treatment in association with butylated hydroxyanisole or dehydroepiandrosterone administration." Jpn.J.Cancer Res.89. 1113-1117 (1998)
[文献書誌] Tsuda,H.et al.: "Co-ordination and ecology in practical cancer prevention." Eur.J.Cancer Prev.7. 409-415 (1998)
[文献書誌] Tsuda,H.et al.: "Chronically elevated proliferation as a risk factor for neoplasia." Eur.J.Cancer Prev.7. 353-385 (1998)
[文献書誌] Tsuda,H.et al.: "European cuntry comparisons provide evidence of a link between colon cancer and adenocarcinoma development in the lung but not the oesophagus." Eur.J.Cancer Prev.7. 473-478 (1998)
[文献書誌] Tsuda,H.et al.: "Inhibitory effects of bovine lactoferrin on intestinal polyposis in the Apc^<Min> mouse." Cancer Lett.134. 141-145 (1998)
[文献書誌] Tsuda,H.et al.: "Cancer associations at the country level and shared risk factors-a fuzzy concept?" Eur.J.Cancer Prev.8. 63-65 (1998)
[文献書誌] Tsuda,H.et al.: "Cancer screening: an educational challenge." Eur.J.Cancer Prev.8. 7-16 (1998)
[文献書誌] Tsuda,H.et al.: "Cross-country comparisons of colon and rectal cancer mortality suggest the exixtence of differences risk factors in eastern and western Europe." Eur.J.Cancer Prev.8. 67-71 (1998)
[文献書誌] Tsuda,H.et al.: "Insulin sensitizers:a promising group of cancer preventive agents?" The Cancer Journal. 11(2). 72-75 (1998)
[文献書誌] Tsuda,H.et al.: "Short/Medium term carcinogenicity tests: simple initiation-promotion assay systems." The use of short-and medium-term tests for carcinogens and data on genetic effects in carcinogenic hazard evaluation.IARC Scientific Publications. 146. 203-249 (1998)
[文献書誌] Tsuda,H.et al.: "Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice." Clinical and Experimental Metastasis. (in press).
[文献書誌] Tsuda,H.et al.: "Marriage of a medium-term liver model to surrogate markers-a practical approach for risk and benefit assessment." Toxicol.Pathol.(in press).
[文献書誌] Ochiya,T.et al.: "Targeting killing of carcinoembryonic antige (CEA)-producing cancer cells by retrivirus displaying a single chain variable fragment antibody." Human Gene Therapy. 9. 235-248 (1998)
[文献書誌] Ochiya,T.et al.: "Molecular cloning and functional analysis of cDNA encoding a rat leukemia inhibitory factor: towards generation of pluripotent rat embryoric stem cells." Oncogene. 16. 3189-3196 (1998)
[文献書誌] Ochiya,T.et al.: "Establishment of poly(ADP-ribose)polymerase-deficient mouse embryonic stem cell lines." Proc.Japan Acad.74. 233-236 (1998)
[文献書誌] Ochiya,T.et al.: "PDGF-receptor is unresponsive to PDGF-AA in aortic smooth muscle cells from the NG2 knockout mouse." J.Cell.Sci.(in press).
[文献書誌] Ochiya,T.et al.: "Poly(ADP-ribose)polymerase gene-disruption conferred mice resistant to streptozocin-induced diabetes." Proc.Natl.Acad.Sci.USA.(in press).
[文献書誌] Ochiya,T.et al.: "Antisense approaches to in vitro organ culture." Antisense Technology,M.Ian Phillips ed.in Methods in Enzymology. (in press).

1998 年度 実績報告書

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

研究代表者

鳥山 弘靖 国立がんセンター, 化学療法部, 研究員 (70156537)

研究成果

[文献書誌] 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)

[文献書誌] Toriyama-Baba,H.et al.: "Enhanced tumorigenicity of rat bladder squamous cell carcinoma cells after abrogation of gap junctional intercellular communication." Jpn.J.Cancer Res.89. 481-486 (1998)

[文献書誌] Toriyama-Baba,H.et al.: "p16 gene overexpression in mouse bladder carcinomas." Cancer Lett.127. 9-13 (1998)

[文献書誌] Toriyama-Baba,H.et al.: "Molecular cloning and function analysis of cDNA encoding a rat leukemia inhibitory factor: towards generation of pluripotent rat embryonic stem cells." Oncogene. 16. 3189-3196 (1998)

[文献書誌] Tsuda,H.et al.: "Implications of the hyperinsulinaemia-diabetes-cancer link for preventive efforts." Eur.J.Cancer Prev.7. 89-107 (1998)

[文献書誌] Tsuda,H.et al.: "Soluble and insoluble fiber influences on cancer development." Oncology Hematology. 27. 229-242 (1998)

[文献書誌] Tsuda,H.et al.: "Physical exercise:a pillar for cancer prevention?" Eur.J.Cancer Prev.7. 177-193 (1998)

[文献書誌] Tsuda,H.et al.: "Orthotopic growth and metastasis of human non-small cell lung carcinoma cells injected into pleural cavity of nude mice." Cancer Lett.127. 203-209 (1998)

[文献書誌] Tsuda,H.et al.: "Cross-country comparisons provide evidence of a strong link between female lung and colon adenocarcinoma development." The Cancer Journal. 11(5). 259-262 (1998)

[文献書誌] Tsuda,H.et al.: "Inhibition of azoxymethane initiated colon tumor and aberrant crypt foci development by bovine lactoferrin administration in F344 rats." Adv.Exp.Med.Biol.443. 273-284 (1998)

[文献書誌] Tsuda,H.et al.: "Histogenetic stereological reconstruction of rat basophilic,Clear and oncocytic neoplastic renal cell lesions using carbonic anhydrase type II-PAS double-stained sections." Toxicol.Pathol.26(6). 769-776 (1998)

[文献書誌] Tsuda,H.et al.: "Co-ordination and ecology in practical cancer prevention." Eur.J.Cancer Prev.7. 409-415 (1998)

[文献書誌] Tsuda,H.et al.: "Chronically elevated proliferation as a risk factor for neoplasia." Eur.J.Cancer Prev.7. 353-385 (1998)

[文献書誌] Tsuda,H.et al.: "European cuntry comparisons provide evidence of a link between colon cancer and adenocarcinoma development in the lung but not the oesophagus." Eur.J.Cancer Prev.7. 473-478 (1998)

[文献書誌] Tsuda,H.et al.: "Inhibitory effects of bovine lactoferrin on intestinal polyposis in the Apc^<Min> mouse." Cancer Lett.134. 141-145 (1998)

[文献書誌] Tsuda,H.et al.: "Cancer associations at the country level and shared risk factors-a fuzzy concept?" Eur.J.Cancer Prev.8. 63-65 (1998)

[文献書誌] Tsuda,H.et al.: "Cancer screening: an educational challenge." Eur.J.Cancer Prev.8. 7-16 (1998)

[文献書誌] Tsuda,H.et al.: "Cross-country comparisons of colon and rectal cancer mortality suggest the exixtence of differences risk factors in eastern and western Europe." Eur.J.Cancer Prev.8. 67-71 (1998)

[文献書誌] Tsuda,H.et al.: "Insulin sensitizers:a promising group of cancer preventive agents?" The Cancer Journal. 11(2). 72-75 (1998)

[文献書誌] Tsuda,H.et al.: "Short/Medium term carcinogenicity tests: simple initiation-promotion assay systems." The use of short-and medium-term tests for carcinogens and data on genetic effects in carcinogenic hazard evaluation.IARC Scientific Publications. 146. 203-249 (1998)

[文献書誌] Tsuda,H.et al.: "Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice." Clinical and Experimental Metastasis. (in press).

[文献書誌] Tsuda,H.et al.: "Marriage of a medium-term liver model to surrogate markers-a practical approach for risk and benefit assessment." Toxicol.Pathol.(in press).

[文献書誌] Ochiya,T.et al.: "Targeting killing of carcinoembryonic antige (CEA)-producing cancer cells by retrivirus displaying a single chain variable fragment antibody." Human Gene Therapy. 9. 235-248 (1998)

[文献書誌] Ochiya,T.et al.: "Molecular cloning and functional analysis of cDNA encoding a rat leukemia inhibitory factor: towards generation of pluripotent rat embryoric stem cells." Oncogene. 16. 3189-3196 (1998)

[文献書誌] Ochiya,T.et al.: "Establishment of poly(ADP-ribose)polymerase-deficient mouse embryonic stem cell lines." Proc.Japan Acad.74. 233-236 (1998)

[文献書誌] Ochiya,T.et al.: "PDGF-receptor is unresponsive to PDGF-AA in aortic smooth muscle cells from the NG2 knockout mouse." J.Cell.Sci.(in press).

[文献書誌] Ochiya,T.et al.: "Poly(ADP-ribose)polymerase gene-disruption conferred mice resistant to streptozocin-induced diabetes." Proc.Natl.Acad.Sci.USA.(in press).

[文献書誌] Ochiya,T.et al.: "Antisense approaches to in vitro organ culture." Antisense Technology,M.Ian Phillips ed.in Methods in Enzymology. (in press).

1998 年度実績報告書

鳥山弘靖国立がんセンター, 化学療法部, 研究員 (70156537)