School of Public Health, 733 University Hall, University of California, Berkeley, CA 94720-7360, USA.
Mutagenesis. 2011 Jan;26(1):51-6. doi: 10.1093/mutage/geq064.
Children may be more susceptible to the effects of the environmental exposure and medical treatments than adults; however, limited information is available about the differences in genotoxic effects in children by age, sex and health status. Micronucleus (MN) assay is a well established method of monitoring genotoxicity, and this approach is thoroughly validated for adult lymphocytes by the Human Micronucleus Biomonitoring project (HUMN.org). Similar international undertaking is in progress for exfoliated buccal cells. Most of the MN studies in children are focused on analyses of lymphocytes but in the recent years, more investigators are interested in using exfoliated cells from the oral cavity and other cell types that can be collected non-invasively, which is particularly important in paediatric cohorts. The baseline MN frequency is relatively low in newborns and its assessment requires large cohorts and cell sample counts. Available results are mostly consistent in conclusion that environmental pollutants and radiation exposures lead to the increase in the MN frequency in children. Effects of medical treatments are less clear, and more studies are needed to optimise the doses and minimise genotoxicity without compromising therapy outcomes. Despite the recent progress in MN assay in children, more studies are warranted to establish the relationship between MN in lymphocytes and exfoliated cells, to clarify sex, age and genotype differences in baseline MN levels and the changes in response to genotoxicants. One of the most important types of MN studies in children are prospective cohorts that will help to clarify the predictive value of MN and other cytome end points for cancer and other chronic diseases of childhood and adulthood. Emerging 'omic' and other novel molecular technologies may shed light on the molecular mechanisms and biological pathways associated with the MN levels in children.
儿童可能比成人更容易受到环境暴露和医疗治疗的影响;然而,关于儿童在年龄、性别和健康状况方面的遗传毒性差异的信息有限。微核(MN)试验是一种监测遗传毒性的成熟方法,并且该方法已经通过人类微核生物监测项目(HUMN.org)对成人淋巴细胞进行了彻底验证。类似的国际工作正在进行中,用于研究脱落的口腔颊细胞。大多数关于儿童的 MN 研究都集中在分析淋巴细胞上,但近年来,越来越多的研究人员对使用口腔脱落细胞和其他可以非侵入性收集的细胞类型感兴趣,这在儿科队列中尤为重要。新生儿的 MN 频率相对较低,其评估需要大的队列和细胞样本计数。现有结果的结论大多一致,即环境污染物和辐射暴露会导致儿童 MN 频率增加。医疗治疗的影响不太清楚,需要更多的研究来优化剂量,在不影响治疗效果的情况下最小化遗传毒性。尽管 MN 试验在儿童中的最新进展,但仍需要更多的研究来建立淋巴细胞和脱落细胞之间的 MN 之间的关系,阐明基线 MN 水平的性别、年龄和基因型差异以及对遗传毒性剂的反应变化。儿童中最重要的 MN 研究之一是前瞻性队列研究,这将有助于阐明 MN 和其他细胞终点对儿童和成人癌症和其他慢性疾病的预测价值。新兴的“组学”和其他新型分子技术可能揭示与儿童 MN 水平相关的分子机制和生物学途径。