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长时间暴露于低浓度化学诱变剂下的人类淋巴母细胞的突变

Mutation of human lymphoblasts exposed to low concentrations of chemical mutagens for long periods of time.

作者信息

Penman B W, Crespi C L, Komives E A, Liber H L, Thilly W G

出版信息

Mutat Res. 1983 Mar;108(1-3):417-36. doi: 10.1016/0027-5107(83)90137-9.

DOI:10.1016/0027-5107(83)90137-9
PMID:6403847
Abstract

Methylnitrosourea (MNU), ethyl methanesulfonate (EMS), and 4-nitroquinoline-N-oxide (4NQO) induce mutation to 6-thioguanine resistance and trifluorothymidine resistance in diploid human lymphoblasts (TK6). In single exposure experiments in which greater than 10% of treated cells survive, mutation as a function of concentration is linear for MNU, accelerates for EMS and appears to reach a plateau for 4NQO. In order to probe the bases of these concentration dependencies, human lymphoblasts were exposed for 20 days to each of the three mutagens. Each individual exposure chosen was in itself insufficient to induce statistically significant mutation and each resulted in a cellular survival of greater than 95%. Under this regimen, induced mutation as a function of the number of exposures was linear for all three mutagens. Prior exposure to low concentrations of mutagens was found to have no significant effect on the amount of mutation induced in subsequent exposures. Thus, no biological evidence was found for the induction of repair of misrepair systems.

摘要

甲基亚硝基脲(MNU)、甲基磺酸乙酯(EMS)和4-硝基喹啉-N-氧化物(4NQO)可诱导二倍体人淋巴母细胞(TK6)对6-硫鸟嘌呤和三氟胸苷产生抗性突变。在单次暴露实验中,当超过10%的处理细胞存活时,MNU的突变率与浓度呈线性关系,EMS的突变率加速上升,而4NQO的突变率似乎达到平台期。为了探究这些浓度依赖性的基础,将人淋巴母细胞分别暴露于这三种诱变剂20天。每次单独暴露本身不足以诱导具有统计学意义的突变,且每次暴露后的细胞存活率均大于95%。在这种方案下,所有三种诱变剂的诱导突变率与暴露次数呈线性关系。发现预先暴露于低浓度诱变剂对后续暴露中诱导的突变量没有显著影响。因此,未发现诱导修复或错配修复系统的生物学证据。

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Mutator/Hypermutable fetal/juvenile metakaryotic stem cells and human colorectal carcinogenesis.突变/高突变性胎儿/幼年亚核干细胞与人类结直肠癌发生
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Possible depletion of a DNA repair enzyme in human lymphoma cells by subversive repair.
通过颠覆性修复可能耗尽人类淋巴瘤细胞中的一种DNA修复酶。
Proc Natl Acad Sci U S A. 1985 Aug;82(16):5285-9. doi: 10.1073/pnas.82.16.5285.
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Evidence for linear response for the induction of mutations in human cells by x-ray exposures below 10 rads.低于10拉德的X射线照射对人类细胞诱变的线性响应证据。
Proc Natl Acad Sci U S A. 1985 Apr;82(7):2092-5. doi: 10.1073/pnas.82.7.2092.
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