School of Medicine and Life Sciences (Department of public health), Nanjing University of Chinese Medicine, 210023, Nanjing, China.
School of Medicine and Life Sciences (Department of public health), Nanjing University of Chinese Medicine, 210023, Nanjing, China.
Mutat Res Rev Mutat Res. 2019 Apr-Jun;780:1-10. doi: 10.1016/j.mrrev.2019.02.002. Epub 2019 Feb 6.
The micronucleus (MN) assay has been used to determine the potential genotoxic effects in human populations exposed to arsenic. Some of these studies found an increase in MN frequency among exposed individuals, but others found no increase or inconclusive results. Thus, the main purpose of this current study was to investigate whether MN can be used as a biomarker for the arsenic exposure, as well as whether or not the different cell types that have been used to monitor MN frequency differ in their sensitivity to upon arsenic exposure. A systematic literature review was conducted followed by a meta-analysis. The review identified 25 useful studies with data from 3232 exposed individuals (15 studies assaying lymphocytes, 16 assaying buccal cells, and 9 assaying urothelial cells), with 18 studies measuring drinking water exposure, 5 measuring occupational exposure, one measuring coal burning, and one measuring dietary exposure. The meta-analysis indicated that the overall estimates of Mean Ratio (MR, defined as the mean value of the response in the exposed group divided by the mean value of the response in the reference group) were 2.95 (95% confidence interval (CI): 2.00 to 4.35), 2.36 (95% CI: 1.77 to 3.15), and 2.82 (95% CI: 1.86 to 4.28) for MN assays conducted with lymphocytes, buccal cells, and urothelial cells in the MN assay, respectively. Subgroup analysis showed that when the exposure method was drinking water, the MN frequencies increased significantly in lymphocytes (MR = 3.59, 95% CI: 2.30 to 5.60), in buccal cells (MR = 2.35, 95% CI: 1.76 to 3.15), and in urothelial cells (MR = 3.16, 95% CI: 2.02 to 4.97). However, when the exposure method was the occupational setting or others, the MN detection using the three types of cells did not find significant differences between groups. Subgroup analysis also showed that lymphocyte MN frequencies increased significantly in both routine-culture MN assays (MR = 2.88, 95% CI: 1.15 to 7.24) and cytokinesis-block MN assays (MR = 2.89, 95% CI: 1.84 to 4.55). The performance of the MN assay with different types of cells was also compared, but no significant differences were found. Therefore, our analysis indicates that MN can be used as an effective biomarker for monitoring arsenic-exposed populations, and that MN assays conducted with lymphocytes, buccal cells, and urothelial cells do not differ in their ability to detect the genetic damage from arsenic.
微核（MN）检测法已被用于评估暴露于砷环境下的人群的潜在遗传毒性效应。部分研究发现暴露组 MN 频率增加，而其他研究则未发现增加或结论不确定。因此，本研究的主要目的是探究 MN 是否可作为砷暴露的生物标志物，以及不同细胞类型检测 MN 频率的敏感性是否存在差异。我们进行了系统文献综述并开展了荟萃分析。综述共纳入 25 项研究，共涉及 3232 名暴露个体的数据（15 项研究检测淋巴细胞，16 项研究检测口腔细胞，9 项研究检测尿路上皮细胞），其中 18 项研究测量饮水暴露，5 项研究测量职业暴露，1 项研究测量燃煤暴露，1 项研究测量饮食暴露。荟萃分析结果显示，总体平均比（MR）估计值（定义为暴露组的反应平均值除以参考组的反应平均值）分别为 2.95（95%置信区间（CI）：2.00 至 4.35）、2.36（95%CI：1.77 至 3.15）和 2.82（95%CI：1.86 至 4.28），用于检测淋巴细胞、口腔细胞和尿路上皮细胞的 MN 试验。亚组分析表明，当暴露方式为饮水时，淋巴细胞（MR=3.59，95%CI：2.30 至 5.60）、口腔细胞（MR=2.35，95%CI：1.76 至 3.15）和尿路上皮细胞（MR=3.16，95%CI：2.02 至 4.97）的 MN 频率显著增加。然而，当暴露方式为职业暴露或其他方式时，三种细胞类型的 MN 检测均未发现组间有显著差异。亚组分析还显示，常规培养 MN 试验（MR=2.88，95%CI：1.15 至 7.24）和细胞分裂阻断 MN 试验（MR=2.89，95%CI：1.84 至 4.55）中淋巴细胞 MN 频率显著增加。我们还比较了不同类型细胞的 MN 试验性能，但未发现显著差异。因此，我们的分析表明 MN 可作为监测砷暴露人群的有效生物标志物，且使用淋巴细胞、口腔细胞和尿路上皮细胞进行 MN 检测在检测砷遗传毒性方面没有差异。
