Gollapudi B Bhaskar, White Paul A, Honma Masamitsu
Exponent, Inc., Health Sciences Center, 1800 Diagonal Road, Alexandria, VA, 22314, USA.
Environmental Health Science and Research Bureau, Health Canada, 50 Colombine Driveway, Ottawa, Ontario, K1A 0K9, Canada.
Mutat Res Genet Toxicol Environ Mutagen. 2019 Dec;848:403061. doi: 10.1016/j.mrgentox.2019.05.017. Epub 2019 May 31.
Assays for gene mutations in cultured mammalian cells, i.e., Mammalian Cell Gene Mutation (MCGM) assays, are widely used in genetic toxicology laboratories worldwide; over the past four decades they have been commonly employed in safety assessment studies, and studies designed to address hypothesis-driven research questions. Despite many advances in the fields of cellular and molecular biology over the past four decades, the MCGM assays commonly used for regulatory evaluations continue to be those developed in the 1970s, including assays that enumerate induced mutations at the hprt or tk loci of several commonly used cell lines. Consequently, the Steering Committee of the 7th International Workshops on Genotoxicity Testing (IWGT) convened a working group (WG) to critically assess the state-of-the-science in regards to the current and emerging tools for the detection of mutagens using cultured mammalian cells. The WG was divided into four sub-groups that evaluated the state-of- the-science with respect to the: (1) in vitro Pig-a gene mutation assay, (2) in vitro assays based on cells from transgenic rodents, (3) technologies and innovations to improve MCGM assays using TK6 cells, and (4) novel and emerging technologies and approaches for detection and enumeration of gene mutations in mammalian cells. Each of these sub-groups critically reviewed the scientific literature, along with other unpublished data, to develop consensus statements on the status of the test systems in their respective focus areas. These reviews, with their associated consensus statements, are presented in the accompanying works by Bemis and Heflich., White et al., Honma et al., and Evans et al. The MCGM assay WG, in consultation with the entire IWGT, formulated consensus statements regarding the overall utility of MCGM assays for identification and assessment of mutagenic hazard.
在培养的哺乳动物细胞中进行基因突变检测，即哺乳动物细胞基因突变（MCGM）检测，在全球遗传毒理学实验室中被广泛应用；在过去的四十年里，它们一直被普遍用于安全性评估研究以及旨在解决假设驱动研究问题的研究中。尽管在过去四十年里细胞和分子生物学领域取得了许多进展，但常用于监管评估的MCGM检测仍然是20世纪70年代开发的那些检测方法，包括对几种常用细胞系的hprt或tk位点诱导突变进行计数的检测方法。因此，第七届遗传毒性测试国际研讨会（IWGT）指导委员会召集了一个工作组（WG），以严格评估使用培养的哺乳动物细胞检测诱变剂的现有和新兴工具的科学现状。该工作组分为四个小组，分别评估以下方面的科学现状：（1）体外Pig-a基因突变检测，（2）基于转基因啮齿动物细胞的体外检测，（3）改进使用TK6细胞的MCGM检测的技术和创新，以及（4）检测和计数哺乳动物细胞基因突变的新兴技术和方法。每个小组都严格审查了科学文献以及其他未发表的数据，以就各自重点领域的测试系统现状制定共识声明。这些审查及其相关的共识声明在Bemis和Heflich、White等人、Honma等人以及Evans等人的相关著作中呈现。MCGM检测工作组与整个IWGT协商，就MCGM检测在识别和评估诱变危害方面的总体效用制定了共识声明。
