1997 Fiscal Year Annual Research Report

環境発がん物質の遺伝子変異特性

Research Project

Project/Area Number	09253255
Research Institution	National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
Principal Investigator	長尾美奈子国立がんセンター, 研究所・発がん研究部, 部長 (40100151)
Co-Investigator(Kenkyū-buntansha)	今井裕国立がんセンター, 研究所・発がん研究部, 研究員 (70300944) 牛島俊和国立がんセンター, 研究所・発がん研究部, 室長 (90232818) 中釜斉国立がんセンター, 研究所・生化学部, 部長 (30198030)
Keywords	PhIP / Apc / β-カテニン / 突然変異スペクトル / p53
Research Abstract	(1)加熱食品中に含まれる発がん物質、2-アミノ-1-メチル-6-フェニルイミダゾ[4,5-b]ピリジン(PhIP)および2-アミノ-3-メチルイミダゾ[4,5-f]キノリン(IQ)で誘発した大腸がんではApc遺伝子に変異のないもの全てにβ-カテニン(Ctnnb1)遺伝子変異が存在し、ラット大腸がんではヒトと同様にWntシグナル伝達系が重要な役割をはたしていることを明らかにした。 (2)PhIP誘発ラット乳がんではCtnnb1遺伝子変異は誘発されていないことを明らかにした。Minマウスでは乳がんが正常マウスに比べ高頻度に誘発されること、Wntがマウスウィルス性乳がんに関与している点からも興味深い知見である。 (3)PhIPの誘発する突然変異のスペクトルをラット大腸およびマウス大腸のlacI遺伝子、チャイニーズハムスター線維芽細胞およびヒトリンパ芽球細胞におけるHprt遺伝子、ヒト線維芽細胞におけるsupF遺伝子変異を用いて検討した結果、PhIPの誘発する突然変異の10%がGGGAからGの欠損であると仮定する事が出来ることがわかった。一方ヒト腫瘍におけるp53突然変異7,400例中22例(0.3%)にGGGAからGの欠失があった。即ちp53突然変異陽性細胞の3%はPhIPによると算出できることがわかった。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Okonogi H., Ushijima T., Nagao,M., et al.: "Induction of aberrant crypt foci in C57BL/6N mice by 2-amino-9H-pyrido[2,3-b]indole (AαC)and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(MelQx)" Cancer Lett.111. 105-109 (1997)
[Publications] Okonogi H., Ushijima,T., Nagao,M., et al.: "Agreement of mutational characteristics of heterocyclic amines in lacI of the Big Blue【O!R】 mouse with those in tumor related genes in rodents" Cancer. 18. 745-748 (1997)
[Publications] Ushijima T., Morimura K., Nagao,M., et al.: "Establishment of methylation-sensitive representational difference analysis and isolation of hypo-and hypermethylated genomic fragments in mouse liver tumors" PROC Natl Acad Sci USA. 94. 2284-2289 (1997)
[Publications] Sanyal R, Darroudi F, Nagao,M. et al.: "Inhibition of the genotoxic effects of heterocyclic amines in human derived hepatoma cells by dietary bioantimutagens" Mutagenesis. 12. 297-303 (1997)
[Publications] Nagao,M., Ushijima,T., et al.: "Genetic changes induced by heterocyclic amines" Mutat Res.376. 161-167 (1997)
[Publications] Weisburger J.H, Hagao,M. et al.: "Modification by dietary fat of mammary gland carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in female SDx F344 F1 hybrid rats" Environ Pathol,Toxicol.Oncol.16. 329-334 (1997)
[Publications] Suzui M., Ushijima T., Nagao,M., et al.: "No involvement of APC gene mutations in ulcerative colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate" Mol Carcinogenesis. 20. 389-393 (1997)
[Publications] Okonogi H., Ushijima,T., Nagao,M., et al.: "Effects of gender and species on spectra of mutation induced by 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine in the lacI transgene" Cancer. 395. 93-99 (1997)
[Publications] Nagao,M., Fujita,H., Ochiai M., et al.: "No direct correlation between mutant frequencies and cancer incidence induced by MeIQ in various organs of Big Blue【O!R】 mice" Mutat Res.(in press). (1997)
[Publications] Dashwood R. H., Suzui M., Nagao,M.et al.: "High Frequency of β-Catenin(ctnnb1)mutations in the colon tumors induced by two heterocyclic amines in the F344 rat" Cancer Research. (in press). (1998)
[Publications] Nagao, M.,Sugimura,T.: "Carcinogenicity : Testing,predicting and interpreting chemical effect" Marcel Dekker,Inc. (in press), (1997)

1997 Fiscal Year Annual Research Report

環境発がん物質の遺伝子変異特性

Principal Investigator

長尾 美奈子 国立がんセンター, 研究所・発がん研究部, 部長 (40100151)

Research Products

[Publications] Okonogi H., Ushijima T., Nagao,M., et al.: "Induction of aberrant crypt foci in C57BL/6N mice by 2-amino-9H-pyrido[2,3-b]indole (AαC)and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline(MelQx)" Cancer Lett.111. 105-109 (1997)

[Publications] Okonogi H., Ushijima,T., Nagao,M., et al.: "Agreement of mutational characteristics of heterocyclic amines in lacI of the Big Blue【O!R】 mouse with those in tumor related genes in rodents" Cancer. 18. 745-748 (1997)

[Publications] Ushijima T., Morimura K., Nagao,M., et al.: "Establishment of methylation-sensitive representational difference analysis and isolation of hypo-and hypermethylated genomic fragments in mouse liver tumors" PROC Natl Acad Sci USA. 94. 2284-2289 (1997)

[Publications] Sanyal R, Darroudi F, Nagao,M. et al.: "Inhibition of the genotoxic effects of heterocyclic amines in human derived hepatoma cells by dietary bioantimutagens" Mutagenesis. 12. 297-303 (1997)

[Publications] Nagao,M., Ushijima,T., et al.: "Genetic changes induced by heterocyclic amines" Mutat Res.376. 161-167 (1997)

[Publications] Weisburger J.H, Hagao,M. et al.: "Modification by dietary fat of mammary gland carcinogenesis induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in female SDx F344 F1 hybrid rats" Environ Pathol,Toxicol.Oncol.16. 329-334 (1997)

[Publications] Suzui M., Ushijima T., Nagao,M., et al.: "No involvement of APC gene mutations in ulcerative colitis-associated rat colon carcinogenesis induced by 1-hydroxyanthraquinone and methylazoxymethanol acetate" Mol Carcinogenesis. 20. 389-393 (1997)

[Publications] Okonogi H., Ushijima,T., Nagao,M., et al.: "Effects of gender and species on spectra of mutation induced by 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine in the lacI transgene" Cancer. 395. 93-99 (1997)

[Publications] Nagao,M., Fujita,H., Ochiai M., et al.: "No direct correlation between mutant frequencies and cancer incidence induced by MeIQ in various organs of Big Blue【O!R】 mice" Mutat Res.(in press). (1997)

[Publications] Dashwood R. H., Suzui M., Nagao,M.et al.: "High Frequency of β-Catenin(ctnnb1)mutations in the colon tumors induced by two heterocyclic amines in the F344 rat" Cancer Research. (in press). (1998)

[Publications] Nagao, M.,Sugimura,T.: "Carcinogenicity : Testing,predicting and interpreting chemical effect" Marcel Dekker,Inc. (in press), (1997)

長尾美奈子国立がんセンター, 研究所・発がん研究部, 部長 (40100151)