Wang Y, Wang Y, Stoner G, You M
Department of Pathology, Medical College of Ohio, Toledo 43699.
Cancer Res. 1993 Apr 1;53(7):1620-4.
Previous studies have demonstrated mutagenic specificity of 2-acetylaminofluorene (AAF) in several strains of bacteria and mammalian cells. Examination of AAF-induced B6C3F1 mouse liver tumor DNAs indicates a G-->T (or C-->A) transversion in the H-ras gene. In the present study, 6 mouse lung tumors [2 were from C3H/HeJ mice and 4 were from (C3H x A/J)F1 mice] and 20 C3H/HeJ mouse liver tumors induced by AAF were analyzed for the presence of activating mutations in the ras gene by utilizing polymerase chain reaction, single-strand conformation polymorphism, and direct DNA sequencing analysis. All of the lung tumors contained an activated K-ras protooncogene with an A-->T transversion at the second base of codon 61. The activating mutations in the H-ras gene were detected in 14 of 20 AAF-induced mouse liver tumors with 13 of 14 having a C-->A transversion at the first base of codon 61 and 1 of 14 having an A-->T transversion at the second base of codon 61. The selectivity of mutations in the ras oncogene observed in AAF-induced mouse lung and liver tumors, as compared to those in spontaneously occurring mouse lung and liver tumors, suggests that AAF may directly induce point mutations in the ras gene. The difference in the ras mutation spectra between lung and liver tumors induced by AAF indicates that AAF mutagenesis could be tissue-specific.
先前的研究已证明2-乙酰氨基芴（AAF）在几种细菌和哺乳动物细胞菌株中的诱变特异性。对AAF诱导的B6C3F1小鼠肝肿瘤DNA的检测表明，H-ras基因中存在G→T（或C→A）颠换。在本研究中，通过聚合酶链反应、单链构象多态性和直接DNA测序分析，对6个小鼠肺肿瘤[2个来自C3H/HeJ小鼠，4个来自（C3H×A/J）F1小鼠]和20个由AAF诱导的C3H/HeJ小鼠肝肿瘤进行分析，以检测ras基因中激活突变的存在。所有肺肿瘤均含有激活的K-ras原癌基因，在密码子61的第二个碱基处发生A→T颠换。在20个由AAF诱导的小鼠肝肿瘤中的14个中检测到H-ras基因的激活突变，其中14个中的13个在密码子61的第一个碱基处发生C→A颠换，14个中的1个在密码子61的第二个碱基处发生A→T颠换。与自发发生的小鼠肺和肝肿瘤相比，在AAF诱导的小鼠肺和肝肿瘤中观察到的ras癌基因突变的选择性表明，AAF可能直接诱导ras基因中的点突变。AAF诱导的肺和肝肿瘤之间ras突变谱的差异表明，AAF诱变可能具有组织特异性。
