マウス膀胱癌におけるp53遺伝子の機能異常の酵母を用いた検索

• Project/Area Number: 12770116
• Research Category: Grant-in-Aid for Encouragement of Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Experimental pathology
• Research Institution: Osaka City University
• Principal Investigator: 森村 圭一朗 大阪市立大学, 大学院・医学研究科, 助手 (30315999)
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥1,900,000 (Direct Cost: ¥1,900,000); Fiscal Year 2001: ¥800,000 (Direct Cost: ¥800,000); Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: マウス膀胱癌 / p53遺伝子 / Yeast Functional Assay / N-butyl-N-(4-hydroxybuthyl)nitrosamine / C3H / He / Shiマウス / NON / 相同染色体分布 / 遺伝子多型 / N-butyl-N-(4-hydroxybutyl)nitrosamine

Research Abstract

化学膀胱発癌感受性の異なる2種類のマウスを親とする2種類のレシプローカルな雄性F1マウスを用い、マウス膀胱癌におけるp53遺伝子変異の相同染色体分布を、酵母を用いた新しい方法で検索した。膀胱発癌感受性の比較的高いNON/Shi(NON)マウスと比較的低いC3H/He/Shi(C3H)マウスをレシプローカルに交配し2種の雄性F1マウスを得た。6週令のこれらのF1マウスにそれぞれN-butyl-N-(4-hydroxybutyl)nitrosamineを0.05%の濃度で12週間にわたって飲料水投与後12週の観察期間をおいた後、発生した膀胱癌を摘出した。発生頻度はC3H×NON群が78%、NON×C3H群が87%であった。p53遺伝子変異異常を検索するにあたり、p53遺伝子変異をその転写活性化能を加味して検索できるYeast Functional Assay法を用いた。また、NONマウスとC3Hマウスの間にはp53遺伝子exon 7 codon 248に多型が認められるため、これをランドマークとして遺伝子変異の相同染色体分布を決定することが可能となる。最終的にC3H×NON群に認められた膀胱癌におけるp53遺伝子変化は89%(8/9)、NON×C3H群では82%(9/11)であった。また、その変異の相同染色体分布はC3H×NON群においてはC3H alleleが33%(3/9),NON alleleが67%(6/9)、NON×C3H群ではC3H alleleが57%(5/9),NON alleleが44%(4/9)であった。P53遺伝子変異はどちらの群においても高率に認められておりマウス膀胱癌発生に重要な役割を果たしていると思われた。現在これらの結果をThe Japanese Journal of Cancer Researchに投稿中である。

Research Products

• [Publications] Salim, E.I.et al.: "Inhibitory Effect of 1,3-diaminopropane, an Ornithine Pecarboxylase Inhibitor, on Rat Two-Stage Urinary Bladder Carcinogenesis initiated by N-buthyl-N-14-hydroxybuthl)nitrosamine"Carcinogenesis. 21. 195-203 (2000)
• [Publications] Iwai, S. et al.: "Possible Drevention by abieslactone of Development of Dietarylnitrosamine-Initiated GST-D positive Foci in the Liver"Teratoge. Carcinog. Mutage. 21. 223-229 (2001)
• [Publications] Okuda, E. et al.: "Detection of p53 Gene mutations in Human Esophageal Squamous Cell Carcinomas Using p53 Yeast Functional Assay : Possible Difference in Esophageal Carcinogenesis Between the Young and the Elder Growth"Clinical. Canere. Res.. 21. 223-229 (2001)
• [Publications] Morimura, K. et al.: "Promotion of Chemically Induced Rat Esophageal Tumorigenesis with Post-initiation Ethanol Modification"Teratoge. Carcinog. Mutage.. 21. 295-301 (2001)
• [Publications] Gen, H.et al.: "p53 and H-ras Mutations and Microsatellite Instability in Renal Pelvic Carcinomas of NON/SHi Mice Treated with N-Buthyl-N-(4hydroxybuthyl)nitorosamine : Different Genetic Alteration from Urinary Bladder Carcinogenesis"Jpn. J. Cancer. Res.. 92. 1278-1283 (2001)
• [Publications] Kinoshita, A. et al.: "Formation of 8-hydroxydeoxyguanosine and cell-cycle arrest in the rat liver via generation of oxidative stress by phenobarbital: association with expression profiles of p21^<WAF1/Cip1>, cyclin D1 and Ogg1"Carcinogenesis. 23. 341-349 (2002)
• [Publications] Morimura,K.: "LOH and mutational analysis of p53 alleles in muose urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl) nitrosamine."Carcinogenesis. 20. 715-718 (1999)
• [Publications] Yamamoto,S.: "Specific p53 gene mutations in urinary bladder epithelium after the Chernobyl accident."Cancer Res.. 59. 3606-3609 (1999)
• [Publications] Chen,T.: "Concentration dependent promoting effects of sodium L-ascorbate with the same total dose in a rat two-stage urinary bladder carcinogenesis."Cancer Lett.. 146. 67-71 (1999)
• [Publications] Salim,E.I.: "Inhibitory effect of 1,3-diaminopropane, an ornithine decarboxylase inhibitor, on rat two-stage urinary bladder carcinogenesis initiated by N-butyl-N-(4-hydroxybutyl) nitrosamine."Carcingenesis.. 21. 195-203 (2000)
• [Publications] Romanenko,A.: "Increased oxidative stress with gene alteration in urinary bladder urothelium after the Chernobyl accident."Int.J.Cancer,. 86. 790-798 (2000)
• [Publications] Wei,M.: "Chemopreventive effects of S-methylcysteine on rat hepatocarcinogenesis induced by concurrent administration of sodium nitrite and morpholine."Cancer Lett.. 161. 97-103 (2000)