K-RAS ONCOGENE MUTATIONS IN RAT COLON TUMORS INDUCED BY N-METHYL-N-NITROSOUREA
K-RAS ONCOGENE MUTATIONS IN RAT COLON TUMORS INDUCED BY N-METHYL-N-NITROSOUREA
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DOI：
10.1093/carcin/13.1.45
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发表时间：
1992-01-01
期刊：
影响因子：
4.7
通讯作者：
BRASITUS, TA
中科院分区：
文献类型：
--
作者：
JACOBY, RF;ALEXANDER, RJ;BRASITUS, TA
我们一直在研究结肠癌的大鼠模型，在该模型中，通过在有限的时间内将N-甲基-N-亚硝基脲（MNU）直接应用于结肠粘膜的离散区域来诱导肿瘤。在许多实验性肿瘤中，包括由MNU诱导的肿瘤，已经观察到ras基因通过点突变的激活。为了检测潜在的激活点突变的H-ras和K-ras癌基因在MNU诱导的大鼠结肠肿瘤，DNA样本从40腺瘤，9个癌，和14个组织学正常组织样本从14只大鼠，以及从16个病灶上诱导的NIH 3 T3细胞的肿瘤DNA-通过聚合酶链反应扩增和杂交等位基因特异性寡核苷酸探针。在这些样本中均未观察到H-ras点突变。然而，我们在4例原发性肿瘤中检测到K-ras基因点突变，1例腺瘤（2.5%）和3例癌（33%）;这些突变都是密码子12和13的第二个核苷酸的G -> A转换。大多数肿瘤中没有可检测到的ras突变表明，与利用MNU的其他动物模型相反，MNU诱导的大鼠结肠肿瘤中的肿瘤发生可能主要涉及ras以外的基因的激活。
We have been studying a rat model of colon cancer in which tumors are induced by direct application of N-methyl-N-nitrosourea (MNU) to discrete areas of the colonic mucosa for a limited period of time. Activation of the ras genes by point mutation has been observed in many experimental tumors, including tumors induced by MNU. To detect potential activating point mutations in the H-ras and K-ras oncogenes in MNU-induced rat colon tumors, DNA samples from 40 adenomas, nine carcinomas, and 14 histologically normal tissue samples from 14 rats-as well as from 16 foci induced on NIH3T3 cells by tumor DNAs-were amplified by the polymerase chain reaction and hybridized with allele-specific oligonucleotide probes. No H-ras point mutations were observed in any of these samples. We did detect K-ras point mutations, however, in four primary tumors-one adenoma (2.5%) and three carcinomas (33%); these mutations were all G --> A transitions at the second nucleotide of codons 12 and 13. The absence of detectable ras mutations from the majority of tumors suggests that, in contrast to other animal models utilizing MNU, tumorigenesis in MNU-induced rat colon tumors may predominantly involve activation of genes other than ras.