Mutagenicity of 5-azacytidine and related nucleosides in C3H/10T 1/2 clone 8 and V79 cells.
Mutagenicity of 5-azacytidine and related nucleosides in C3H/10T 1/2 clone 8 and V79 cells.
复制标题
C3H/10T 1/2 克隆 8 和 V79 细胞中 5-氮杂胞苷和相关核苷的致突变性。
作者：
J. Landolph;P. Jones
为了确定5-氮杂胞苷（5-AzaCR）诱导的C3 H/10 T 1/2克隆B（10 T 1/2）细胞转化和/或分化是否可能具有突变基础，我们研究了5-AzaCR和结构相关的核苷类似物是否可以使10 T 1/2和中国仓鼠V79细胞突变。在10 T 1/2细胞中哇巴因抗性突变的测定中，其检测碱基置换突变但不检测移码突变，5-AzaCR和6-氮杂胞苷没有显著致突变性。5-氮杂-2 '-脱氧胞苷、5-氟-2'-脱氧胞苷、5，6-二氢-5-氮杂胞苷、5-氟-2 '-脱氧尿苷（FUdR）、5-溴-2'-脱氧尿苷（BUdR）和1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）仅具有弱致突变性。在V79细胞中哇巴因耐药性突变的测定中，该测定还检测碱基取代突变，但不检测移码突变，5-AzaCR、5-氮杂-2 '-脱氧胞苷、FUdR和ara-C没有可检测到的致突变性，而BUdR在高细胞毒性浓度下具有中度致突变性。在V79细胞中检测碱基置换和移码突变的8-氮鸟嘌呤抗性突变试验中，5-氟-2 '-脱氧胞苷和ara-C具有弱致突变性，BUdR在极高细胞毒性浓度下具有中度致突变性，5-AzaCR、5-氮杂-2'-脱氧胞苷、FUdR、6-氮杂胞苷和5，6-二氢-5-氮杂胞苷无显著致突变性。因此，5-AzaCR和相关胞嘧啶类似物的致突变性可忽略不计。这项研究并没有为5-AzaCR诱导10 T 1/2细胞分化的突变基础提供支持。此外，核苷5-AzaCR，ara-C，BUdR和FUdR的致突变性与其先前报道的转化10 T 1/2细胞的能力之间没有相关性。5-AzaCR和FUdR的致突变性很低，这些效应的生物学意义尚不确定。因此，尚不清楚突变在多大程度上（如果有的话）有助于这两种化合物引起的转化，还应研究其他可能的转化机制。
To determine whether 5-azacytidine (5-AzaCR)-induced transformation and/or differentiation of C3H/10T 1/2 clone B (10T 1/2) cells might have a mutational basis, we studied whether 5-AzaCR and structurally related nucleoside analogs could mutate 10T 1/2 and Chinese hamster V79 cells. In an assay for mutation to ouabain resistance in 10T 1/2 cells, which detects base substitution mutations but not frameshift mutations, 5-AzaCR and 6-azacytidine were not significantly mutagenic. 5-Aza-2'-deoxycytidine, 5-fluoro-2'-deoxycytidine, 5,6-dihydro-5-azacytidine, 5-fluoro-2'-deoxyuridine (FUdR), 5-bromo-2'-deoxyuridine (BUdR), and 1-beta-D-arabinofuranosylcytosine (ara-C) were only weakly mutagenic. In an assay for mutation to ouabain resistance in V79 cells, which also detects base substitution mutations but not frameshift mutations, 5-AzaCR, 5-aza-2'-deoxycytidine, FUdR, and ara-C were not detectably mutagenic, and BUdR was moderately mutagenic at highly cytotoxic concentrations. In an assay for mutation to 8-azaguanine resistance in V79 cells, which detects base substitution and frameshift mutations, 5-fluoro-2'-deoxycytidine and ara-C were weakly mutagenic, BUdR was moderately mutagenic at very cytotoxic concentrations, and 5-AzaCR, 5-aza-2'-deoxycytidine, FUdR, 6-azacytidine, and 5,6-dihydro-5-azacytidine were not significantly mutagenic. Therefore, 5-AzaCR and related cytosine analogs can be considered as negligibly mutagenic. This study does not provide support for a mutational basis for 5-AzaCR-induced differentiation in 10T 1/2 cells. Further, there was no correlation between the mutagenicity of the nucleosides 5-AzaCR, ara-C, BUdR, and FUdR studied here and their previously reported abilities to transform 10T 1/2 cells. The mutagenicities of 5-AzaCR and FUdR were so low that the biological significance of these effects is uncertain. Hence, it is not clear to what extent, if any, mutation contributes to the transformation caused by these two compounds, and other possible mechanisms of transformation should also be investigated.