【摘要】目的检测甲基亚硝基脲诱导大鼠大肠肿瘤中抑癌基因p 53变化 。方法应用PCR，SSCP和SSCP和DNA测序的方法。结果经PCR-SSCP分析，可见甲基亚硝 基脲诱导大鼠大肠肿瘤中，出现p53基因单链的移位条带，且在第VII外显子；进一步 做双链直 接测序分析，见到p53蛋白编码序列的第244密码子的第3碱基C缺失。结论 实验结果提 示大鼠暴露于致癌物甲基亚硝基脲后，产生了大肠肿瘤，且在分子水平上见到了抑癌基因p5 3突变。

【中图分类号】Q754；Q95-33【文献标识码】A【文章编号】0529-1356(2000)增-97

RAT P53GENE MUTATIONS IN THE COLORECTAL TUMORS INDUCED BY N-METHYL-N-NITROSOUREA

LI Jia-hui

(Institute of Laboratory Animal,CAMS and PUMC,Beijing 100021，China;)

GAO Ai-ling

(the People's Hospital,Linfen 04100,China;)

FU Song-bin,LI Pu,LIU Zhi-cheng

(Harbin Medical University,Harbin 150086,China)

【Abstract】Objective We have examined tumor suppressor gen e p53 from N-methy1-N-nitrosourea(MNU)induced the colorectal tumors in rats. Methods PCR,SSCP and DNA sequence analysis.Results In c olorectal tumors induced by MNU,the mobility shifts of p53 gene mutation w ere obse rved,p53 gene mutation was a deletion at third position C of codon 244 in exon7. Conclusion The present study suggested that MNU induces rat p53 mutations in the colorectal tumors.

【Key words】MNU; Colorectal tumors; p53gnen mutation

【基金项目】黑龙江省自然科学基金资助项目(94016)

【作者简介】李佳慧(1961-)，女(汉族)，辽宁省丹东市人，博士后

参考文献

［1］ Nigro JM,Jessup JM,Hostetter R,et al.Mutations in the p53 ge ne oc cur in diverse human tumour types［J］.Nature,1989,342(6250):705-708.

［2］ Hollstein M,Sidransky D,Vogelstein B,et al.p53 mutations in human carcer［J］.Science,1991,253(5015):49-43.

［3］ Finlay CA,Hinds PW,Levine AJ.The p53 proto-oncogene can act as a suppressor of transformation［J］.Cell,1989,57(7):1083-1093.

［4］ Rideout WM,Coetzee GA, Olumi AF,et al.5-Methylcytosine as an muta gen in the human LDL receptor and p53 genes［J］.Science,1990,249(4974):1288-1 290.

［5］ Sambrook J,Fritsch EF,Maniatis T.Molecular Cloning［M］.New York: Cold Spring Harbor Laboratory Press,1989,9：16-23.

［6］ Halevy O,Rodel J,Peled A,et al.Frequent p53 mutations in che mically induced murine fibrosarcoma［J］,Oncogene,1991,6(9):1593-600.

［7］ Makino H,Ishizaka Y,Tsujimoto A,et al.Rat p⁵3 gene mutations in primary Zymbal gland tumors induced by 2-amino-3-methylimidazo［4,5-f］ qui noline,a food mutagen［J］.Proc Natl Acad Sci,1992,89(11):4850-4854.

［8］ Ohgaki H,Hard GC,Hirota N,et al.Selective mutatin of codons 204 an d 213 of the p53 gene in rat tumors induced by alkylating N-Nitroso compounds［J ］.Cancer Res,1992,52(10):2995-2998.

［9］ Recio L,Sisk S,Pluta L,et al.p53 muations in formaldehyde in duced nasal squamous cell carcinomas in rats［J］.Cancer Res,1992,52(21):6113-6116 .

【收稿日期】2000-07-17【修回日期】2000-08-24