Exposures to nanomaterials (NMs), with their specific physico-chemical characteristics, are likely to increase over the next years, as their production for industrial, consumer and medical applications is steadily rising. Therefore, there is an urgent need for the implementation of human biomonitoring studies of genotoxic effects after NM exposures in order to monitor and assure safety for workers and the general population. In this review, most commonly used biomarkers of early genetic effects were analyzed for their adequacy after NM exposures. A more in depth analysis of the ex vivo/in vitro lymphocyte MN assay was performed, although, in literature no studies are available using this assay for NM exposures. Therefore, the known factors determining the NMs tissue/cellular targets and the multiplicity of modes of action of NMs were summarized. The main pending questions are whether (1) lymphocytes are a NM target or an adequate surrogate tissue, (2) whether the buccal MN assay might be more suitable for NM exposures via inhalation or ingestion, as buccal cells might be exposed more directly. While the current state-of-the-art does not allow for drawing firm conclusions, major research gaps are identified and some cautious recommendations can be formulated. Therefore in vitro and in vivo studies should be conducted comparing methodologies side-by-side in the same subjects and for different types of NMs. The ex vivo/in vitro MN assay in its automated version, allowing objective analysis of large cohorts and detection of direct and indirect genotoxic effects, remains a valuable candidate for human biomonitoring to NM exposure. Considering the potential cancer risk from exposure to NMs and previous dramatic experiences with too late surveillance of occupational exposures to similar substances (e.g. to asbestos), there is an urgent need to define and implement adequate scientifically sound biomonitoring methods and programme for exposure to NMs.

中文翻译：

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对人类暴露于纳米材料的遗传毒性作用的生物监测：未来的挑战。

随着其用于工业，消费和医疗应用的生产稳定增长，在未来几年中，具有特定物理化学特征的纳米材料（NMs）暴露量可能会增加。因此，迫切需要对人体暴露于NM后进行遗传毒性作用的人体生物监测研究，以监测和确保工人和普通民众的安全。在这篇综述中，分析了NM暴露后最常用的早期遗传效应生物标志物的适当性。进行了更深入的离体/体外淋巴细胞MN检测分析，尽管在文献中，尚无使用该检测方法进行NM暴露的研究。因此，总结了决定NMs组织/细胞靶标的已知因素以及NMs作用方式的多样性。尚待解决的主要问题是：（1）淋巴细胞是NM的靶标还是足够的替代组织；（2）颊MN检测是否更适合通过吸入或摄入进行NM暴露，因为颊细胞可能更直接地暴露。尽管当前的最新技术无法得出明确的结论，但可以确定主要的研究空白，并可以提出一些谨慎的建议。因此，应该在同一受试者中以及针对不同类型的NM进行并排比较方法学的体外和体内研究。自动化版本的离体/体外MN分析可对大型队列进行客观分析，并检测直接和间接的基因毒性作用，仍然是人类对NM暴露进行生物监测的有价值的候选者。