Relationship between somatic mutation and neoplastic transformation.
Relationship between somatic mutation and neoplastic transformation.
复制标题
体细胞突变与肿瘤转化的关系。
DOI：
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发表时间：
1978
影响因子：
11.1
通讯作者：
P. Ts'o
中科院分区：
文献类型：
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作者：
J. Barrett;P. Ts'o
同时检测了叙利亚仓鼠二倍体胚胎细胞的体细胞突变和肿瘤转化。在次黄嘌呤磷酸核糖转移酶和Na（+）/K（+）ATP酶位点定量苯并[a]芘和N-甲基-N '-硝基-N-亚硝基胍诱导的突变，并与通过细胞形态学变化和琼脂中集落形成测量的表型转化进行比较。这两种细胞转化的特点不同的体细胞突变观察到的两个位点。形态转化后观察到的时间与体细胞突变，但在频率是25- 540倍高。转化子在琼脂上的菌落形成频率为10（-5）-10（-6），但在致癌剂处理后32-75个群体倍增数才能检测到。虽然这种转化的频率与体细胞突变的频率相当，但所需的检测时间比常规研究的体细胞突变的最佳表达时间长得多。仓鼠胚胎细胞的肿瘤转化被描述为一个多步骤的渐进过程。致癌物处理后细胞的各种表型转化可能代表了这种进行性转化的不同阶段。结果进行了讨论，在这种情况下，诱变在不同阶段之间的过渡中的作用被认为是。肿瘤性转化可能由突变引起，但不能完全用涉及显性、共显性或X连锁隐性基因座的单基因突变事件来描述。化学致癌物诱导的肿瘤转化比单个基因突变过程更为复杂。因此，这项比较研究并没有提供实验支持的基础上，从传统的体细胞突变试验获得的结果的简单外推化学品的致癌潜力的预测。
Somatic mutation and neoplastic transformation of diploid Syrian hamster embryo cells were examined concomitantly. Mutations induced by benzo[a]pyrene and N-methyl-N'-nitro-N-nitrosoguanidine were quantitated at the hypoxanthine phosphoribosyltransferase and Na(+)/K(+) ATPase loci and compared to phenotypic transformations measured by changes in cellular morphology and colony formation in agar. Both cellular transformations had characteristics distinct from the somatic mutations observed at the two loci. Morphological transformation was observed after a time comparable to that of somatic mutation but at a frequency that was 25- to 540-fold higher. Transformants capable of colony formation in agar were detected at a frequency of 10(-5)-10(-6), but not until 32-75 population doublings after carcinogen treatment. Although this frequency of transformation is comparable to that of somatic mutation, the detection time required is much longer than the optimal expression time of conventionally studied somatic mutations. Neoplastic transformation of hamster embryo cells has been described as a multistep, progressive process. Various phenotypic transformations of cells after carcinogen treatment may represent different stages in this progressive transformation. The results are discussed in this context and the role of mutagenesis in the transition between various stages is considered. Neoplastic transformation may be initiated by a mutational change, but it cannot be described completely by a single gene mutational event involving a dominant, codominant, or X-linked recessive locus. Neoplastic transformation induced by chemical carcinogens is more complex than a single gene mutational process. Thus, this comparative study does not give experimental support to predictions of the carcinogenic potential of chemicals based on a simple extrapolation of the results obtained from conventional somatic mutation assays.