Food Safety Research Institute, Nissin Foods Holdings Co., Ltd., 7-4-1 Nojihigashi, Kusatsu, Shiga 525-0058, Japan.
Mutat Res. 2011 Sep 18;724(1-2):76-85. doi: 10.1016/j.mrgentox.2011.06.003. Epub 2011 Jun 17.
Genotoxicity assessment is important for predicting the carcinogenicity of chemical substances. p53R2 is a p53-regulated gene that is induced by various genotoxic stresses. We previously developed a p53R2-dependent luciferase reporter gene assay in the MCF-7 human breast adenocarcinoma cell line, and demonstrated its ability to detect genotoxic agents. In this paper, we investigate the applicability of the p53R2-based genotoxicity test in the human lymphoblastoid cell line TK6. TK6 cells that express wild-type p53 have been widely used for genetic toxicology studies. To evaluate the performance of the test system in TK6 cells, we referred to 61 of the chemicals on the list of 20 genotoxic and 42 non-genotoxic chemicals recommended for the evaluation of modified or new mammalian cell genotoxicity tests by the European Centre for the Validation of Alternative Methods. The overall accordance, sensitivity, and specificity of our results with the ECVAM list were 90% (55/61), 85% (17/20), and 93% (38/41), respectively. These results indicate that the p53R2-based genotoxicity test can detect various types of genotoxic chemicals without compromising its specificity. This test will be a valuable tool for rapid screen for identifying chemicals that may be genotoxic to humans.
遗传毒性评估对于预测化学物质的致癌性非常重要。p53R2 是一种受多种遗传毒性应激诱导的 p53 调节基因。我们之前在 MCF-7 人乳腺腺癌细胞系中开发了一种依赖于 p53R2 的荧光素酶报告基因检测方法，并证明了其检测遗传毒性剂的能力。在本文中，我们研究了基于 p53R2 的遗传毒性试验在人淋巴母细胞系 TK6 中的适用性。表达野生型 p53 的 TK6 细胞已被广泛用于遗传毒理学研究。为了评估测试系统在 TK6 细胞中的性能，我们参考了欧洲替代方法验证中心推荐用于评估改良或新型哺乳动物细胞遗传毒性试验的 20 种遗传毒性和 42 种非遗传毒性化学物质清单中的 61 种化学物质。我们的结果与 ECVAM 清单的总体一致性、敏感性和特异性分别为 90%（55/61）、85%（17/20）和 93%（38/41）。这些结果表明，基于 p53R2 的遗传毒性试验可以检测各种类型的遗传毒性化学物质，而不会影响其特异性。该试验将成为快速筛选可能对人类具有遗传毒性的化学物质的有价值工具。
