实验设计因素对基因毒物体外试验效力的影响。

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY
Mutagenesis Pub Date : 2022-12-08 DOI:10.1093/mutage/geac025
Julie Sanders, Anouck Thienpont, Roel Anthonissen, Tamara Vanhaecke, Birgit Mertens
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引用次数: 1

摘要

以往的研究表明,实验设计因素的差异可能会改变体外基因毒性试验中基因毒性化合物的效价。这些研究大多采用基于最低观察到的遗传毒性效应水平的传统统计方法,而更合适的方法,如基准剂量(BMD)方法,现在可用于比较不同试验条件下的遗传毒性效力。因此,我们在体外微核(MN)试验和彗星试验(CA)中研究了两个参数,即细胞类型和暴露时间对两种已知基因毒物[黄曲霉毒素B1和甲磺酸乙酯(EMS)]效力的影响。两种化合物在两种检测中使用两种细胞类型(即CHO-K1和TK6细胞)进行测试。为了评估暴露时间的影响,在暴露3 h和24 h后评估EMS的遗传毒性。结果采用骨密度协变量法进行分析,也称为骨密度效价排序,并将结果与基于最低观察到的遗传毒性效应水平的更传统的统计方法进行比较。当将两种细胞系的体外MN结果与BMD共变量方法进行比较时,仅在EMS暴露24小时时才检测到效力差异,其中TK6细胞更敏感。两种细胞系体外CA中EMS和黄曲霉毒素B1的效力均无差异。相比之下,在所有测试条件下,即在体外MN测定和两种细胞系的CA中,EMS在24小时暴露后比暴露3小时更有效。重要的是,对于一些被调查的因素,BMD协变量方法不能用于确认用传统统计方法检测到的效力差异,因此强调需要用适当的方法评估实验设计因素的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of experimental design factors on the potency of genotoxicants in in vitro tests.

Previous studies have shown that differences in experimental design factors may alter the potency of genotoxic compounds in in vitro genotoxicity tests. Most of these studies used traditional statistical methods based on the lowest observed genotoxic effect levels, whereas more appropriate methods, such as the benchmark dose (BMD) approach, are now available to compare genotoxic potencies under different test conditions. We therefore investigated the influence of two parameters, i.e. cell type and exposure duration, on the potencies of two known genotoxicants [aflatoxin B1 and ethyl methanesulfonate (EMS)] in the in vitro micronucleus (MN) assay and comet assay (CA). Both compounds were tested in the two assays using two cell types (i.e. CHO-K1 and TK6 cells). To evaluate the effect of exposure duration, the genotoxicity of EMS was assessed after 3 and 24 h of exposure. Results were analyzed using the BMD covariate approach, also referred to as BMD potency ranking, and the outcome was compared with that of more traditional statistical methods based on lowest observed genotoxic effect levels. When comparing the in vitro MN results obtained in both cell lines with the BMD covariate approach, a difference in potency was detected only when EMS exposures were conducted for 24 h, with TK6 cells being more sensitive. No difference was observed in the potency of both EMS and aflatoxin B1 in the in vitro CA using both cell lines. In contrast, EMS was more potent after 24 h exposure compared with a 3 h exposure under all tested conditions, i.e. in the in vitro MN assay and CA in both cell lines. Importantly, for several of the investigated factors, the BMD covariate method could not be used to confirm the differences in potencies detected with the traditional statistical methods, thus highlighting the need to evaluate the impact of experimental design factors with adequate approaches.

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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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