Induction of micronuclei in human cell lines and primary cells by combination treatment with gamma-radiation and ethyl methanesulfonate.
Induction of micronuclei in human cell lines and primary cells by combination treatment with gamma-radiation and ethyl methanesulfonate.
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通过伽马辐射和甲磺酸乙酯的联合处理在人类细胞系和原代细胞中诱导微核。
DOI：
10.1093/mutage/17.2.177
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发表时间：
2002
期刊：
影响因子：
2.7
通讯作者：
W. Lutz
中科院分区：
文献类型：
--
作者：
H. Stopper;W. Lutz
虽然遗传毒性测试通常是对单一化学品进行的，但人类的接触往往涉及多种物质的组合。该实验室先前的结果显示，在用来自137 Cs源的γ辐射和甲磺酸乙酯（EMS）联合处理后，p53突变小鼠淋巴瘤L5178 Y细胞中微核诱导具有超加和性。现在的问题是，超加和性是否是物理和化学DNA损伤剂组合的遗传毒性的一般现象，或者结果是否具有物种和细胞类型特异性。在两种人淋巴母细胞样细胞系TK 6（野生型p53）和WTK 1（突变型p53）以及来自胎儿人肺的原代成纤维细胞中研究了相同的药物组合。剂量在线性剂量效应范围内，导致微核增加至对照组的1.5- 3倍。辐射剂量在125和350 mGy之间，而EMS浓度对于细胞系为20-50 μ g/ml，对于原代细胞为250-350 μ g/ml。在所有人体试验系统中均未观察到超加和性。对于WTK 1细胞，其在p53状态方面与小鼠细胞最相似，甚至存在亚加性组合效应的趋势。对小鼠细胞差异的可能解释可能与物种特异性方面、p53突变的不同后果或其他突变的存在有关。结论是，在解释和推断混合物毒性数据的实验结果时应谨慎，因为结果可能对特定的药剂、剂量和测定方法具有高度特异性。
While testing for genotoxicity is usually performed on single chemicals, exposure of humans often involves combinations of agents. Previous results from this laboratory showed supra-additivity for the induction of micronuclei in p53-mutated mouse lymphoma L5178Y cells after combined treatment with gamma-radiation from a 137Cs source and ethyl methanesulfonate (EMS). The question now was whether supra-additivity was a general phenomenon for the genotoxicity of this combination of a physical and a chemical DNA-damaging agent or whether the result was species- and cell type-specific. The same combination of agents was investigated in two human lymphoblastoid cell lines, TK6 (wild-type p53) and WTK1 (mutated p53), and primary fibroblasts from a fetal human lung. Doses were in the linear dose-effect range, resulting in a 1.5- to 3-fold increase in micronuclei above control. Radiation doses were between 125 and 350 mGy, while the EMS concentrations were 20-50 microg/ml for the cell lines and 250-350 microg/ml for the primary cells. In none of the human test systems was supra-additivity observed. With the WTK1 cells, which are most similar to the mouse cells regarding p53 status, there was even a tendency for a sub-additive combination effect. Possible explanations for the difference to the mouse cells could be related to species-specific aspects, different consequences of the p53 mutations or the presence of additional mutations. It is concluded that caution is advised in the interpretation and extrapolation of experimental results of mixture toxicity data because the outcome could be highly specific for the given selection of agents, doses and assays.
通过杂合性缺失 (LOH) 和整个 11 号染色体染色分析大和小菌落 L5178Y tk-/- 小鼠淋巴瘤突变体：重组检测。
影响因子：
2.7
作者：
Liechty,MC;Scalzi,JM;Sims,KR;CrosbyJr,H;Spencer,DL;Davis,LM;Caspary,WJ;Hozier,JC
通讯作者：
Hozier,JC
影响因子：
3.4
作者：
CORNFORTH, MN;BEDFORD, JS
通讯作者：
BEDFORD, JS