Unit of Environmental Carcinogenesis Ospedale Policlinico San Martino, Genova, Italy.
Unit of Clinical Epidemiology, Ospedale Policlinico San Martino Genova, Italy.
Sci Total Environ. 2019 Feb 20;652:513-522. doi: 10.1016/j.scitotenv.2018.10.187. Epub 2018 Oct 15.
The micronucleus test in peripheral blood lymphocytes is the most widely validated technique to evaluate the DNA damage and chromosomal instability in human populations. The test is largely applied in monitoring environmental and occupational exposure to genotoxic agents. It was also proposed as a biomarker of risk/susceptibility for cancer and other degenerative diseases. The availability of "normal values" in healthy populations is a main requisite for the assay application in human biomonitoring. Age and gender-related ranges of micronucleated binucleated cells (MNBN) baseline values were established in a group of 103 healthy platelet donors (50 males and 53 females) not recently exposed to genotoxic agents and characterized for demographic, lifestyle and dietary factors. Repeatability of the test by the same scorer was evaluated. Reproducibility was estimated through analysis of repeated blood samples. High correlation between the results of the three blood samplings in two separate scoring sessions of MNBN/1000BN (R values were 0.83, 0.74 and 0.68; P < 0.0001) and PI values (R values were 0.69, 0.62 and 0.65; P < 0.0001) was detected. High consistency among the values obtained in three different samplings in the same individual was observed (Intraclass Correlation Coefficient (ICC) = 0.905, (95% CI = 0.868-0.933, P < 0.0001) The range of "normal" values predicted on the basis of the results of the present study appears to be sufficiently narrow to warrant application of the assay in the comparison of data obtained from groups of exposed or susceptible subjects, supporting its use in preventive programs. The large inter-individual variability predicted by the model used in the present study hampers a clinical application of the assay at individual level. The method applied in the present study represents a generally applicable model to derive "normal values" in any population, as an essential step before starting a biomonitoring study.
外周血淋巴细胞微核试验是评估人群 DNA 损伤和染色体不稳定性最广泛验证的技术。该试验广泛应用于监测环境和职业接触遗传毒性剂。它也被提议作为癌症和其他退行性疾病风险/易感性的生物标志物。在人类生物监测中应用该测定法的一个主要要求是获得健康人群的“正常值”。在一组未接触遗传毒性剂的 103 名健康血小板供体(50 名男性和 53 名女性)中,建立了微核双核细胞(MNBN)基线值的年龄和性别相关范围,并对其进行了人口统计学、生活方式和饮食因素的特征描述。通过同一评分员评估了该试验的重复性。通过分析重复的血液样本来评估重现性。在两次单独的 MNBN/1000BN 评分中,三次采血的结果之间存在高度相关性(R 值分别为 0.83、0.74 和 0.68;P<0.0001)和 PI 值(R 值分别为 0.69、0.62 和 0.65;P<0.0001)。在同一个体的三次不同采血中获得的数值高度一致(组内相关系数(ICC)=0.905,(95%CI=0.868-0.933,P<0.0001)。基于本研究结果预测的“正常值”范围似乎足够窄,可以在比较暴露或易感人群的数据时应用该测定法,支持其在预防计划中的应用。本研究中使用的模型预测的个体间差异很大,限制了该测定法在个体水平上的临床应用。本研究中应用的方法代表了一种普遍适用的模型,可以在开始生物监测研究之前,在任何人群中得出“正常值”。