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甲磺酸海蒽酮诱导的L5178Y大、小集落小鼠淋巴瘤细胞突变体中TK基因座的分子分析

Molecular analysis of the TK locus in L5178Y large and small colony mouse lymphoma cell mutants induced by hycanthone methanesulfonate.

作者信息

el-Tarras A, Dubins J S, Warner J, Hoffman C, Cobb R R

机构信息

Life Sciences and Toxicology, Research Triangle Institute, Research Triangle Park, NC 27709, USA.

出版信息

Mutat Res. 1995 Nov;332(1-2):89-95. doi: 10.1016/0027-5107(95)00157-6.

DOI:10.1016/0027-5107(95)00157-6
PMID:7500995
Abstract

Mouse lymphoma cells of the L5178Y TK + /-3.7.2C line were exposed to varying concentrations of the anti-schistosomal drug hycanthone methanesulfonate. The trifluorothymidine (TFT)-resistant cells fell into two classes based on colony size. Southern blot analyses were performed using NcoI-digested DNA from a number of large and small mutant colonies from each treatment group. Two different restriction fragment banding patterns were identified in these analyses, those colonies that contained the 6.4 kb NcoI restriction fragment and those that did not. A total of 471 mutant colonies were analyzed and 84.5% (398) of these colonies did not exhibit the 6.4 kb fragment. There did not appear to be a hycanthone methanesulfonate dose response effect in the number of colonies that did not contain the 6.4 kb fragment among the treated groups. In addition, 82% (154 out of 188) of spontaneous mutants did not contain the 6.4 kb fragment. The results imply that greater than 80% of all spontaneous mutations found in the mouse lymphoma assay regardless of colony size do not contain the 6.4 kb fragment and each may be considered to be a large scale mutation. In addition, greater than 80% of the hycanthone induced mutations in the mouse lymphoma assay do not contain the 6.4 kb fragment and thus may be considered to be a large scale mutation.

摘要

将L5178Y TK + /-3.7.2C系的小鼠淋巴瘤细胞暴露于不同浓度的抗血吸虫药物甲磺酸海蒽酮中。根据集落大小,耐三氟胸苷(TFT)的细胞分为两类。使用来自每个处理组的多个大、小突变集落的经NcoI消化的DNA进行Southern印迹分析。在这些分析中鉴定出两种不同的限制性片段条带模式,即含有6.4 kb NcoI限制性片段的集落和不含有该片段的集落。总共分析了471个突变集落,其中84.5%(398个)的集落未显示出6.4 kb的片段。在处理组中,不含6.4 kb片段的集落数量似乎没有甲磺酸海蒽酮剂量反应效应。此外,82%(188个中的154个)的自发突变体不含有6.4 kb片段。结果表明,在小鼠淋巴瘤试验中发现的所有自发突变中,无论集落大小,超过80%的突变不含有6.4 kb片段,每个突变都可被视为大规模突变。此外,在小鼠淋巴瘤试验中,超过80%的海蒽酮诱导突变不含有6.4 kb片段,因此可被视为大规模突变。

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