Chromosomal changes: induction, detection methods and applicability in human biomonitoring.

2.50
Hdl Handle:
http://hdl.handle.net/10146/25492
Title:
Chromosomal changes: induction, detection methods and applicability in human biomonitoring.
Authors:
Mateuca, R.; Lombaert, N.; Aka, P.V.; Decordier, I.; Kirsch-Volders, M.
Abstract:
The objective of this state of the art paper is to review the mechanisms of induction, the fate, the methodology, the sensitivity/specificity and predictivity of two major cytogenetic endpoints applied for genotoxicity studies and biomonitoring purposes: chromosome aberrations and micronuclei. Chromosomal aberrations (CAs) are changes in normal chromosome structure or number that can occur spontaneously or as a result of chemical/radiation treatment. Structural CAs in peripheral blood lymphocytes (PBLs), as assessed by the chromosome aberration (CA) assay, have been used for over 30 years in occupational and environmental settings as a biomarker of early effects of genotoxic carcinogens. A high frequency of structural CAs in lymphocytes (reporter tissue) is predictive of increased cancer risk, irrespective of the cause of the initial CA increase. Micronuclei (MN) are small, extranuclear bodies that arise in dividing cells from acentric chromosome/chromatid fragments or whole chromosomes/chromatids that lag behind in anaphase and are not included in the daughter nuclei in telophase. The cytokinesis-block micronucleus (CBMN) assay is the most extensively used method for measuring MN in human lymphocytes, and can be considered as a "cytome" assay covering cell proliferation, cell death and chromosomal changes. The key advantages of the CBMN assay lie in its ability to detect both clastogenic and aneugenic events and to identify cells which divided once in culture. Evaluation of the mechanistic origin of individual MN by centromere and kinetochore identification contributes to the high sensitivity of the method. A number of findings support the hypothesis of a predictive association between the frequency of MN in cytokinesis-blocked lymphocytes and cancer development. Recent advances in fluorescence in situ hybridization (FISH) and microarray technologies are modifying the nature of cytogenetics, allowing chromosome and gene identification on metaphase as well as in interphase. Automated scoring by flow cytometry and/or image analysis will enhance their applicability.
Citation:
Biochimie 2006, 88 (11):1515-1531
Journal:
Biochimie
Issue Date:
Nov-2006
URI:
http://hdl.handle.net/10146/25492
DOI:
10.1016/j.biochi.2006.07.004
PubMed ID:
16919864
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRJ-4KJTM8Y-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=df7701ccc8cba66df17bd01f39853bac
Type:
Article
Language:
en
ISSN:
0300-9084
Sponsors:
This work was partly supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (Contract No 513943) and partly supported by NewGeneris (Newborns and Genotoxic Exposure Risks), an integrated research project operating within the same EU Framework Program, Priority 5 (Contract No 016320- 2).
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Full metadata record

DC FieldValue Language
dc.contributor.authorMateuca, R.-
dc.contributor.authorLombaert, N.-
dc.contributor.authorAka, P.V.-
dc.contributor.authorDecordier, I.-
dc.contributor.authorKirsch-Volders, M.-
dc.date.accessioned2008-05-12T09:21:32Z-
dc.date.available2008-05-12T09:21:32Z-
dc.date.issued2006-11-
dc.identifier.citationBiochimie 2006, 88 (11):1515-1531en
dc.identifier.issn0300-9084-
dc.identifier.pmid16919864-
dc.identifier.doi10.1016/j.biochi.2006.07.004-
dc.identifier.urihttp://hdl.handle.net/10146/25492-
dc.description.abstractThe objective of this state of the art paper is to review the mechanisms of induction, the fate, the methodology, the sensitivity/specificity and predictivity of two major cytogenetic endpoints applied for genotoxicity studies and biomonitoring purposes: chromosome aberrations and micronuclei. Chromosomal aberrations (CAs) are changes in normal chromosome structure or number that can occur spontaneously or as a result of chemical/radiation treatment. Structural CAs in peripheral blood lymphocytes (PBLs), as assessed by the chromosome aberration (CA) assay, have been used for over 30 years in occupational and environmental settings as a biomarker of early effects of genotoxic carcinogens. A high frequency of structural CAs in lymphocytes (reporter tissue) is predictive of increased cancer risk, irrespective of the cause of the initial CA increase. Micronuclei (MN) are small, extranuclear bodies that arise in dividing cells from acentric chromosome/chromatid fragments or whole chromosomes/chromatids that lag behind in anaphase and are not included in the daughter nuclei in telophase. The cytokinesis-block micronucleus (CBMN) assay is the most extensively used method for measuring MN in human lymphocytes, and can be considered as a "cytome" assay covering cell proliferation, cell death and chromosomal changes. The key advantages of the CBMN assay lie in its ability to detect both clastogenic and aneugenic events and to identify cells which divided once in culture. Evaluation of the mechanistic origin of individual MN by centromere and kinetochore identification contributes to the high sensitivity of the method. A number of findings support the hypothesis of a predictive association between the frequency of MN in cytokinesis-blocked lymphocytes and cancer development. Recent advances in fluorescence in situ hybridization (FISH) and microarray technologies are modifying the nature of cytogenetics, allowing chromosome and gene identification on metaphase as well as in interphase. Automated scoring by flow cytometry and/or image analysis will enhance their applicability.en
dc.description.sponsorshipThis work was partly supported by ECNIS (Environmental Cancer Risk, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: "Food Quality and Safety" (Contract No 513943) and partly supported by NewGeneris (Newborns and Genotoxic Exposure Risks), an integrated research project operating within the same EU Framework Program, Priority 5 (Contract No 016320- 2).en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VRJ-4KJTM8Y-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=df7701ccc8cba66df17bd01f39853bacen
dc.subjectChromosomal aberrationen
dc.subjectMicronucleien
dc.subjectFluorescence in situ hybridizationen
dc.subjectGenetic polymorphismsen
dc.subject.meshCell Division-
dc.subject.meshChromosome Aberrations-
dc.subject.meshEnvironmental Monitoring-
dc.subject.meshHumans-
dc.subject.meshNeoplasms-
dc.subject.meshSmoking-
dc.titleChromosomal changes: induction, detection methods and applicability in human biomonitoring.en
dc.typeArticleen
dc.identifier.journalBiochimieen

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