Micronuclei frequency in children exposed to environmental mutagens: a review

https://doi.org/10.1016/j.mrrev.2003.06.009Get rights and content

Abstract

Cytogenetic monitoring has been traditionally used for the surveillance of populations exposed to genotoxic agents. In recent years sensitivity problems emerged in surveys of populations exposed to low levels of mutagens, and therefore alternative approaches have been explored. Biomonitoring studies in children are a promising field, since because of evident differences in the uptake, metabolism, distribution and excretion of mutagens this population seems to be more susceptible than adults. Further, the effect of major confounders such as cigarettes smoking, occupation, life-style, and dietary factors plays a minor role. Among cytogenetic assays, the micronucleus assay (MN) has several advantages and is increasingly used. A review was then carried out to synthesize the published data on the occurrence of MN in children and adolescents (age range 0–18 years), and to assess the impact of genotoxic exposure on MN frequency. Overall, 20 papers from international literature and 8 Russian papers were included. An effect of age was found within this age range, while the influence of gender on MN frequency was irrelevant. These results were confirmed by the re-analysis of data for 448 children selected from the HUMN database. An effect of chronic and infectious diseases on MN levels has been reported by various authors. Most studies describing the effect of exposure to genotoxic agents (ionizing radiation, chemicals, drugs, environmental tobacco smoke) found an increase of MN in exposed children. The limited number of published papers indicates that the conduct of properly designed studies on the effect of environmental pollutants in children may be difficult. This review confirmed the usefulness of MN assay in biomonitoring studies conducted in children, revealing that in many circumstances investigating children increases the sensitivity of the study, even with low dose exposures.

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).

References (36)

  • N.N Ilyinskikh et al.

    Micronucleus test of erythrocytes and lymphocytes in the blood of the Altai region residents living near the Semipalatinsk atomic proving ground

    Mutat. Res.

    (1997)
  • Nordic Study Group on the Health Risk of Chromosome Damage, A Nordic data base on somatic chromosome damage in humans,...
  • S Bonassi et al.

    Chromosomal aberrations in lymphocytes predict human cancer indipendently of exposure to carcinogens

    Cancer Res.

    (2000)
  • L.M Anderson et al.

    Critical windows of exposure for children’s health: cancer in human epidemiological studies and neoplasms in experimental animal models

    Environ. Health Perspect.

    (2000)
  • J.G Gurney et al.

    Trends in cancer incidence among children in the US

    Cancer

    (1996)
  • J Olsen

    Significance of prenatal exposure for long-term health effects

    Lakartidningen

    (2001)
  • S Bonassi et al.

    HUman MicroNucleus project: international database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes. I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei

    Environ. Mol. Mutagen

    (2001)
  • R Barale et al.

    Sister chromatid exchange and micronucleus frequency in human lymphocytes of 1,650 subjects in an Italian population. II. Contribution of sex, age, and lifestyle

    Environ. Mol. Mutagen

    (1998)
  • Cited by (102)

    • A critical review on genotoxicity potential of low dimensional nanomaterials

      2021, Journal of Hazardous Materials
      Citation Excerpt :

      Adriamycin, an anthracycline drug, has been found to increase MN frequency up to 10- to 15-fold and significantly decrease cell survival with strong mutagenic properties (Bhuyan et al., 1983; Jagetia and Nayak, 2000). Neri et al. reported that common genotoxic agents, including ionizing radiation, air pollution, and chemical drugs, would affect the children causing an increase in MN (Neri et al., 2003). When compared to the comet assay, the MN assay is more reliable, faster, and easier for the measurement of genotoxicity detecting the chromosomal loss or disruption of the mitotic apparatus (Balasubramanyam et al., 2009a; Ren et al., 2017).

    • Buccal micronucleus cytome assay in primary school children: A descriptive analysis of the MAPEC_LIFE multicenter cohort study

      2018, International Journal of Hygiene and Environmental Health
      Citation Excerpt :

      The results of this study confirm the increased risk of chromosomal alterations in epithelial buccal cells associated with the presence of smokers in the children’s house. MN frequency was positively associated with mother smoking habits in season II (late-spring), in the absence of residential heating; this result is in line with a 30% or more increase in MN frequency in children exposed to cigarette smoke with respect to those unexposed (Neri et al., 2003; Holland et al., 2011). A high adherence of children’s dietary habits to Mediterranean diet was associated with lower MN frequency, supporting a possible association between dietary habits and MN frequency, which is still under discussion for both adults and children (Bonassi et al., 2011a).

    • Metal toxicity assessment by sentinel species of mangroves: In situ case study integrating chemical and biomarkers analyses

      2017, Ecotoxicology and Environmental Safety
      Citation 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).

    • Multi-level biological responses in Ucides cordatus (Linnaeus, 1763) (Brachyura, Ucididae) as indicators of conservation status in mangrove areas from the western atlantic

      2016, Ecotoxicology and Environmental Safety
      Citation 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.

    View all citing articles on Scopus
    View full text