Micronuclei frequency in children exposed to environmental mutagens: a review
Introduction
Cytogenetic monitoring has been traditionally used for the surveillance of populations exposed to environmental mutagens including ionizing radiation (IR), chemicals and life-style factors, and to medical treatments. The validity of these studies has been reinforced by recent findings from European cohort studies, which have validated chromosomal aberrations as predictors of cancer risk, supporting their use in populations exposed to genotoxic agents [1], [2].
Children, as developing individuals, may express increased susceptibility to environmental hazards due to differences in the uptake, metabolism, distribution and excretion of mutagens. This hypothesis is mostly supported by epidemiological findings, reporting increasing trends of cancer incidence in children, and by experimental data showing an increased risk of cancer in rodents exposed in utero to carcinogens as compared to exposure occurring at mature age [3]. Specifically, the incidence of leukemia and central nervous system cancers has significantly increased in the US, Canada, and parts of Europe [4]. Although an increased incidence may reflect improvements in diagnosis, intrauterine and postnatal exposure to environmental xenobiotics is considered to be etiologically relevant [5].
Biomonitoring studies in children are affected to a lower extent by confounders like cigarette smoking and drinking habits, occupational exposure and life-style (mainly dietary factors), which are factors of great concern in adults. Conversely, the role played by infectious diseases in pediatric populations needs to be carefully taken into account. Among the bioassays used to evaluate the impact of environmental, genetic and life-style factors on genomic stability in humans, the micronucleus assay (MN) has gained increased attention, and a growing number of studies have been published. The key advantage of the MN assay is the relative ease of scoring, the limited costs and person-time required, and the precision obtained from scoring larger numbers of cells. MN is generally performed in peripheral blood lymphocytes (PBL) and, to a lesser extent, in epithelial cells, erythrocytes, alveolar macrophages and fibroblasts.
This systematic review performed within the framework of the ChildrenGenoNetworkEuropean Community funded program aims at: (1) summarizing the available data on the occurrence of MN in different tissues in children (age range 0–18 years) exposed to known or suspected environmental mutagens or medical treatments; and (2) to assess the role of these exposures in MN frequency while accounting for the effect of individual host factors, and potential confounders.
Section snippets
Review protocol and search strategy
Individuals from newborns to late adolescence (age range 0–18 years) were considered as children. The choice of this age range allowed, theoretically, the evaluation of potential effects of hormonal changes occurring during puberty and that of cigarette smoking, often starting immediately after adolescence. All published studies were identified by systematically searching the MedLine database (US National Library of Medicine). The search strategy was the following: the term “Micronucleus Tests”
Effect of host factors and confounding variables
We found 14 studies evaluating the effect of gender and/or age on MN. Some of them have been specifically designed for this purpose while others included MN frequency by age and gender as secondary study outcome.
Conclusions
The present review of MN studies in children exposed to environmental mutagens reveals the very limited application of the MN assay to detect early biological outcomes of exposures to environmental genotoxic agents. The review provides important information that should be considered in the design of studies on environmental pollutants, such as the need to control for confounding factors, to understand the impact of effect modifiers of the exposure–effect relations, and to define the appropriate
Acknowledgements
The study was supported by grants funded by the Associazione Italiana per la Ricerca sul Cancro (AIRC) and the European Union 5th FP (QLRT-2001-02831 and QLRT-2001-02198).
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2017, Ecotoxicology and Environmental SafetyCitation Excerpt :Thus, to estimate these alterations, many authors have used the technique of micronucleated cells, expressed in MN‰ (Scarpato et al., 1990; Brunetti et al., 1988; Al-Sabti and Metcalfe, 1995; Burgeot et al., 1995; Hoshina et al., 2008; Collier et al., 2013; Pinheiro et al., 2013), as well as the neutral red technique, quantified through the retention time of the neutral red (NRRT) in lysosomes (Lowe et al., 1995; Svendsen et al., 2004; Daguano et al., 2007). These techniques have large ecological importance for populations of affected areas (Bonassi et al., 2000; Neri et al., 2003; Duarte et al., 2016), having been applied in freshwater (Falfushynska et al., 2014; Taylor et al., 2017), estuarine (Pereira et al., 2014; Duarte et al., 2016) and marine environments (Catharino et al., 2008; Buratti et al., 2012; Wyatt et al., 2014). The use of biological models (bioindicators) may reveal "sentinel" species, named so because of early metal toxicity detection in natural environments, some of them having an important ecosystem function (Beltrame et al., 2010, 2011; Pereira et al., 2014).
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2016, Ecotoxicology and Environmental SafetyCitation Excerpt :Genetic and physiological changes are therefore of particular importance, since they are conspicuous in organisms that inhabit impacted areas (Adams, 1990; Dailianis et al., 2003; Otomo and Reinecke, 2010; Amiard-Triquet et al., 2013; Toufexia et al., 2013). Because of their effectiveness and ecological relevance (Bonassi et al., 2000; Dailianis et al., 2003; Neri et al., 2003), two biomarker assays are widely used. The first is the micronucleus test (MN‰), which quantifies the frequency of micronucleated cells and which measures genotoxicity.