Molecular and cellular mechanisms of transformation of C3H/10T1/2 Cl 8 and diploid human fibroblasts by unique carcinogenic, nonmutagenic metal compounds. A review.
Molecular and cellular mechanisms of transformation of C3H/10T1/2 Cl 8 and diploid human fibroblasts by unique carcinogenic, nonmutagenic metal compounds. A review.
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独特的致癌、非诱变金属化合物转化 C3H/10T1/2 Cl 8 和二倍体人成纤维细胞的分子和细胞机制。
DOI：
10.1007/bf02917289
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发表时间：
1989
影响因子：
3.9
通讯作者：
Landolph,JR
中科院分区：
文献类型：
--
作者：
Landolph,JR
我们实验室的工作表明，致癌金属盐砷、镍和铬诱导培养的C3 H/10 T1/2Cl 8（10 T1/2）小鼠胚胎细胞的形态转化，许多转化体在软琼脂中生长并在裸鼠体内形成肿瘤。砷、镍和铬化合物诱导形态转化的浓度不会诱导10 T1/2细胞突变为哇巴因抗性。这表明，金属诱导的形态学转化的机制可能不是由诱导碱基置换突变引起的，在铬酸铅的情况下，可能不是由移码或缺失突变引起的。此外，我们表明，致癌的砷，镍，铬化合物，和MNNG，诱导锚定在二倍体人成纤维细胞的独立性。来源于锚定非依赖性集落的锚定非依赖性细胞株是稳定的，但不形成病灶，并最终衰老，因此，砷和镍化合物和铬酸铅诱导稳定的锚定非依赖性作为一个孤立的表型。镍化合物和铬酸铅诱导锚定的独立性，但不突变哇巴因抗性或6-硫鸟嘌呤抗性。因此，这些金属盐在人成纤维细胞中诱导锚定独立性的机制可能不是通过诱导这些突变试验中测量的碱基取代、移码或缺失突变。另一方面，MNNG在诱导锚定独立性的相同浓度范围内诱导突变为6-硫鸟嘌呤抗性和哇巴因抗性，表明MNNG可能通过诱导碱基取代、移码或缺失突变来诱导锚定独立性。因此，在鼠和人碱基取代突变中，金属盐的机制可能诱导形态学和锚定独立的转化。我们推测，原癌基因的重排或扩增，或抑癌基因的失活，可能在金属盐诱导的10 T1/2和二倍体人成纤维细胞的形态或锚定独立转化的机制中发挥作用。* 直接支持 * A03 GS 019 00027
Work from our laboratory showed that carcinogenic metal salts of arsenic, nickel, and chromium induced morphological transformation of cultured C3H/10T1/2Cl 8 (10T1/2) mouse embryo cells, and that many of the transformants grow in soft agarose and form tumors in nude mice. Concentrations of arsenic, nickel, and chromium compounds that induced morphological transformation did not induce mutation to ouabain resistance in 10T1/2cells. This indicated that the mechanism of metal induced morphological transformation was likely not caused by induction of base substitution mutations, and in the case of lead chromate, likely not caused by frameshift or deletion mutations.In addition, we showed that carcinogenic arsenic, nickel, and chromium compounds, and MNNG, induced anchorage independence in diploid human fibroblasts. Anchorage-independent cell strains derived from anchorage-independent colonies were stable but did not form foci and eventually senesced, therefore, arsenic and nickel compounds and lead chromate induced stable anchorage independence as an isolated phenotype. Nickel compounds and lead chromate induced anchorage independence but not mutation to ouabain resistance or to 6-thioguanine resistance. Hence, the mechanism of induction of anchorage independence by these metal salts in human fibroblasts was likely not via induction of base substitution, frameshift, or deletion mutations that would be measured in these mutation assays. MNNG, on the other hand, induced mutation to 6-thioguanine resistance and to ouabain resistance over the same concentration ranges that induced anchorage independence was induced, indicating that MNNG might induce anchorage independence by inducing base substitution, frameshift, or deletion mutations. It is likely, therefore that the mechanisms of metal salt induced morphological and anchorage independent transformation in murine and human base substitution mutations. We hypothesize that rearrangements or amplification of proto-oncogenes, or, possibly, inactivation of suppressoro oncogenes, might play a role in the mechanism of metal salt induced morphological or anchorage independent transformation of 10T1/2and diploid human fibroblasts, respectively. *** DIRECT SUPPORT *** A03GS019 00027