Baseline Micronuclei Frequency in Children: Estimates from Meta- and Pooled Analyses

The number of studies evaluating the effect of environmental exposure to genotoxic agents in children has rapidly increased in the last few years. The frequency of micronuclei (MN) in peripheral blood lymphocytes determined with the cytokinesis block assay is among the most popular biomarkers used for this purpose, although large inter- and intralaboratory variability of this end point has been observed in population studies. The availability of reference measures is therefore necessary for laboratories to validate protocols and analytical procedures, and for molecular epidemiologists, as well, to estimate the statistical power of studies and to assess the quality of data. In this article, we provide estimates of the baseline frequency of MN in children, conducting a meta-analysis of MN frequency reported by field studies in children and a pooled analysis of individual data [available from published studies and from the Human Micronucleus International Collaborative Study (HUMN) database]. Thirteen articles were selected for meta-analysis, and individual data included in the pooled analysis were retrieved from the databases of 12 laboratories. Overall means of 4.48 [95% confidence interval (CI), 3.35–5.98] and 5.70 (95% CI, 4.29–7.56) MN per 1,000 binucleated cells were estimated by the meta- and pooled analysis, respectively. A clear effect of age was detected, even within the restricted range of pediatric age considered, with significantly lower frequency values in newborns. No influence of sex was found. The study showed the advantage of using data from large collaborative studies and suggested a synergistic use of meta- and pooled analysis

Chromosomal aberration frequency in lymphocytes predicts the risk of cancer: results from a pooled cohort study of 22 358 subjects in 11 countries

Mechanistic evidence linking chromosomal aberration (CA) to early stages of cancer has been recently supported by the results of epidemiological studies that associated CA frequency in peripheral lymphocytes of healthy individuals to future cancer incidence. To overcome the limitations of single studies and to evaluate the strength of this association, a pooled analysis was carried out. The pooled database included 11 national cohorts and a total of 22 358 cancer-free individuals who underwent genetic screening with CA for biomonitoring purposes during 1965–2002 and were followed up for cancer incidence and/or mortality for an average of 10.1 years; 368 cancer deaths and 675 incident cancer cases were observed. Subjects were classified within each laboratory according to tertiles of CA frequency. The relative risk (RR) of cancer was increased for subjects in the medium [RR = 1.31, 95% confidence interval (CI) = 1.07–1.60] and in the high (RR = 1.41; 95% CI = 1.16–1.72) tertiles when compared with the low tertile. This increase was mostly driven by chromosome-type aberrations. The presence of ring chromosomes increased the RR to 2.22 (95% CI = 1.34–3.68). The strongest association was found for stomach cancer [RRmedium = 1.17 (95% CI = 0.37–3.70), RRhigh = 3.13 (95% CI = 1.17–8.39)]. Exposure to carcinogens did not modify the effect of CA levels on overall cancer risk. These results reinforce the evidence of a link between CA frequency and cancer risk and provide novel information on the role of aberration subclass and cancer type

Children's exposure to environmental pollutants and biomarkers of genetic damage. I. Overview and critical issues.

In the last decade, molecular epidemiological studies have provided new perspectives on studying environmental risks in pediatric populations, based on the growing understanding that children may be more susceptible to toxicants than adults. Protecting children’s health is a social priority, and specific research programs have been initiated with this purpose in the United States and Europe. These programs address the development of (i) less invasive methods for biological specimens collection, (ii) specific tools for interpretation and validation of biomarkers, (iii) methods for translating biomarker results into intervention strategies and for integrating them with environmental monitoring and health data, (iv) optimal ways to obtain consent and provide information to children and/or their parents participating in the studies and (v) techniques for the effective communication with policy makers and the public. Critical issues in children’s environmental research discussed in this paper include specific needs of study design, exposure assessment, sample collection and ethics. Special consideration is given to the autonomy of the child in giving consent, the details and nature of the information provided, and the need to warrant controlled access to sensitive information. The use of incentives such as gifts and payment to ensure the participation of school-aged children is specifically discussed. Examples of field studies that are focused on the effects of pesticides, air pollution and formaldehyde are used to illustrate advantages and limitations of biomarker studies in children

Emissions generated by sugarcane burning promote genotoxicity in rural workers: a case study in Barretos, Brazil

Background: To determine the possible genotoxic effect of exposure to the smoke generated by biomass burning on workers involved in manual sugar cane harvesting. Methods: The frequency of micronuclei in exfoliated buccal cells and peripheral blood lymphocytes was determined in sugarcane workers in the Barretos region of Brazil, during the harvest season and compared to a control population, comprised of administrative employees of Barretos Cancer Hospital. Results: The frequency of micronuclei was higher in the sugar cane workers. The mean frequency in blood lymphocytes (micronuclei/1000 cells) in the test group was 8.22 versus 1.27 in the control group. The same effect was observed when exfoliated buccal cells were considered (22.75 and 9.70 micronuclei/1000 cells for sugar cane workers and controls, respectively). Conclusion: Exposure to emissions produced by the burning of sugar cane during harvesting induces genomic instability in workers, indicating the necessity of adopting more advanced techniques of harvesting sugar cane to preserve human health.We thank the Researcher Support Center of Barretos Cancer Hospital, especially the statistician Zanardo C. for assisting in the statistical analysis. We thank Oliveira R. for technical support, and we acknowledge financial support from FAPESP Proc. 2010/10192-6

Mumificaçao fetal em suínos associada à toxoplasmose.

bitstream/item/58346/1/CUsersPiazzonDocuments271.pd

Genetic susceptibility to malignant pleural mesothelioma and other asbestos-associated diseases.

Exposure to asbestos fibers is a major risk factor for malignant pleuralmesothelioma (MPM), lung cancer, and other non-neoplastic conditions, such as asbestosis and pleural plaques. However, in the last decade many studies have shown that polymorphism in the genes involved in xenobiotic and oxidative metabolism or in DNA repair processes may play an important role in the etiology and pathogenesis of these diseases. To evaluate the association between diseases linked to asbestos and genetic variability we performed a review of studies on this topic included in the PubMed database. One hundred fifty-nine citations were retrieved; 24 of them met the inclusion criteria and were evaluated in the review. The most commonly studied GSTM1 polymorphism showed for all asbestos-linked diseases an increased risk in association with the null genotype, possibly linked to its role in the conjugation of reactive oxygen species. Studies focused on GSTT1 null and SOD2 Ala16Val polymorphisms gave conflicting results, while promising results came from studies on a1-antitrypsin in asbestosis and MPO in lung cancer. Among genetic polymorphisms associated to the risk of MPM, the GSTM1 null genotype and two variant alleles of XRCC1 and XRCC3 showed increased risks in a subset of studies. Results for the NAT2 acetylator status, SOD2 polymorphism and EPHX activity were conflicting. Major limitations in the study design, including the small size of study groups, affected the reliability of these studies. Technical improvements such as the use of high-throughput techniques will help to identify molecular pathways regulated by candidate genes

Commentary: Critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals - a HUMN project perspective

Abstract not availableMicheline Kirsch-Volders, Stefano Bonassi, Siegfried Knasmueller, Nina Holland, Claudia Bolognesi, Michael F. Fenec