当前位置: X-MOL 学术Mutat. Res. Fund. Mol. Mech. Mutagen. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Analysis of chemical structures and mutations detected by Salmonella TA98 and TA100
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis ( IF 2.3 ) Pub Date : 2023-09-30 , DOI: 10.1016/j.mrfmmm.2023.111838
Kevin P Cross 1 , David M DeMarini 2
Affiliation  

As part of an analysis performed under the auspices of the International Workshop on Genotoxicity Testing (IWGT) in 2017, we and others showed that Salmonella frameshift strain TA98 and base-substitution strain TA100 together + /- S9 detected 93% of the mutagens detected by all the bacterial strains recommended by OECD TG471 (Williams et al., Mutation Res. 848:503081, 2019). We have extended this analysis by identifying the numbers and chemical classes of chemicals detected by these two strains either alone or in combination, including the role of S9. Using the Leadscope 2021 SAR Genetox database containing > 21,900 compounds, our dataset containing 7170 compounds tested in both TA98 and TA100. Together, TA98 and TA100 detected 94% (3733/3981) of the mutagens detected using all the TG471-recommended bacterial strains; 39% were mutagenic in one or both strains. TA100 detected 77% of all of these mutagens and TA98 70%. Considering the overlap of detection by both strains, 12% of these mutagens were detected only by TA98 and 19% only by TA100. In the absence of S9, sensitivity dropped by 31% for TA98 and 29% for TA100. Overall, 32% of the mutagens required S9 for detection by either strain; 9% were detected only without S9. Using the 2021 Leadscope Genetox Expert Alerts, TA100 detected 18 mutagenic alerting chemical classes with better sensitivity than TA98, whereas TA98 detected 10 classes better than TA100. TA100 detected more chemical classes than did TA98, especially hydrazines, azides, various di- and tri-halides, various nitrosamines, epoxides, aziridines, difurans, and half-mustards; TA98 especially detected polycyclic primary amines, various aromatic amines, polycyclic aromatic hydrocarbons, triazines, and dibenzo-furans. Model compounds with these structures induce primarily G to T mutations in TA100 and/or a hotspot GC deletion in TA98. Both TA98 and TA100 + /- S9 are needed for adequate mutagenicity screening with the Salmonella (Ames) assay.



中文翻译:

沙门氏菌TA98和TA100检测的化学结构和突变分析

作为 2017 年国际基因毒性测试研讨会 (IWGT) 主持下进行的分析的一部分,我们和其他人表明,沙门氏菌移码菌株 TA98 和碱基取代菌株 TA100 一起+/- S9 检测到了 93% 的诱变剂。 OECD TG471 推荐的所有细菌菌株(Williams 等人,Mutation Res. 848:503081, 2019)。我们通过确定这两种菌株单独或组合检测到的化学物质的数量和化学类别(包括 S9 的作用)来扩展此分析。使用包含超过 21,900 种化合物的 Leadscope 2021 SAR Genetox 数据库,我们的数据集包含在 TA98 和 TA100 中测试的 7170 种化合物。TA98 和 TA100 总共检测到了使用所有 TG471 推荐的细菌菌株检测到的 94% (3733/3981) 的诱变剂;39% 的一种或两种菌株具有诱变性。TA100 检测到了所有这些诱变剂的 77%,TA98 检测到了 70%。考虑到两种菌株检测的重叠,其中 12% 的诱变剂仅由 TA98 检测到,19% 仅由 TA100 检测到。在缺少 S9 的情况下,TA98 的灵敏度下降了 31%,TA100 的灵敏度下降了 29%。总体而言,其中 32% 的诱变剂需要 S9 才能通过任一菌株进行检测;仅在没有 S9 的情况下检测到 9%。使用 2021 年 Leadscope Genetox 专家警报,TA100 检测到 18 种诱变警报化学物质,其灵敏度比 TA98 更高,而 TA98 检测到的 10 种物质比 TA100 更好。TA100 比 TA98 检测到更多的化学类别,特别是、叠氮化物、各种二卤化物和三卤化物、各种亚硝胺、环氧化物、氮丙啶、二呋喃和半芥子;TA98特别检测多环伯胺、各种芳香胺、多环芳香烃、三嗪和二苯并呋喃。具有这些结构的模型化合物主要诱导 TA100 中的 G 到 T 突变和/或 TA98 中的热点 GC 缺失。TA98 和 TA100 +/- S9 都需要通过沙门氏菌(Ames) 检测进行充分的致突变性筛查

更新日期:2023-09-30
down
wechat
bug