Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, 00166 Rome, Italy.
Mutat Res Rev Mutat Res. 2016 Oct-Dec;770(Pt A):140-161. doi: 10.1016/j.mrrev.2016.03.003. Epub 2016 Mar 6.
Various metals have demonstrated genotoxic and carcinogenic potential via different mechanisms. Until now, biomonitoring and epidemiological studies have been carried out to assess the genotoxic risk to exposed human populations. In this sense, the use of the micronucleus assay in peripheral blood lymphocytes has proven to be a useful tool to determine increased levels of DNA damage, as a surrogate biomarker of cancer risk. Here we review those biomonitoring studies focused on people exposed to arsenic, chromium, nickel, vanadium and complex mixtures of metals. Only those studies that used the frequency of micronuclei in binucleated (BNMN) cells have been taken into consideration, although the inclusion of other biomarkers of exposure and genotoxicity are also reflected and discussed. Regarding arsenic, most of the occupational and environmental biomonitoring studies find an increase in BNMN among the exposed individuals. Thus, it seems conclusive that arsenic exposure increases the risk of exposed human populations. However, a lack of correlation between the level of exposure and the increase in BNMN is also common, and a limited number of studies evaluated the genotype as a risk modulator. As for chromium, a BNMN increase in occupationally exposed subjects and a correlation between level of exposure and effect is found consistently in the available literature. However, the quality score of the studies is only medium-low. On the other hand, the studies evaluating nickel and vanadium are scarce and lacks a correct characterization of the individual exposure, which difficult the building of clear conclusions. Finally, several studies with medium-high quality scores evaluated a more realistic scenario of exposure which takes into account a mixture of metals. Among them, those which correctly characterized and measured the exposure were able to find association with the level of BNMN. Also, several genes associated with DNA damage repair such as OGG1 and XRCC1 were found to influence the exposure effect.
各种金属通过不同的机制表现出遗传毒性和致癌性。到目前为止,已经进行了生物监测和流行病学研究,以评估暴露人群的遗传毒性风险。在这方面,外周血淋巴细胞微核试验已被证明是一种有用的工具,可以确定 DNA 损伤水平升高,作为癌症风险的替代生物标志物。在这里,我们回顾了那些针对接触砷、铬、镍、钒和金属混合物的人群进行的生物监测研究。仅考虑了那些使用双核细胞(BNMN)中微核频率的研究,尽管也反映和讨论了其他暴露和遗传毒性的生物标志物。关于砷,大多数职业和环境生物监测研究发现暴露个体中 BNMN 的增加。因此,似乎可以得出结论,砷暴露会增加暴露人群的风险。然而,暴露水平与 BNMN 增加之间缺乏相关性也很常见,并且很少有研究评估基因型作为风险调节剂。至于铬,在职业暴露的人群中发现 BNMN 增加,并且在现有文献中一致发现暴露水平与效应之间存在相关性。然而,研究的质量评分仅为中低水平。另一方面,评估镍和钒的研究很少,并且缺乏对个体暴露的正确描述,这使得难以得出明确的结论。最后,几项质量评分中等偏上的研究评估了一种更现实的暴露情景,其中考虑了金属混合物。其中,那些正确描述和测量暴露的研究能够发现与 BNMN 水平的关联。此外,还发现了一些与 DNA 损伤修复相关的基因,如 OGG1 和 XRCC1,它们会影响暴露效应。