Chromosomal damage

Raluca Mateuca (born Teodorescu), Micheline Volders

    Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

    Abstract

    Chromosomal aberrations (CAs) are changes in normal chromosome structure
    or number that can occur spontaneously or as a result of chemical or radiation
    treatment [1]. Structural CAs in peripheral blood lymphocytes (PBLs) have been used
    for over 30 years in occupational and environmental settings as a biomarker of early
    effects of genotoxic carcinogens [2] (see Section 2.3.1.). Structural CAs are most
    commonly scored in meta-phase-arrested cells that have been fixed, spread
    on microscope slides, and Giemsa stained [3]. However, this method is not suitable
    for estimation of numerical CAs as artefactual chromosome loss may occur and its use
    for this purpose will not be considered here3.
    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 [4].
    Micronuclei represent a measure of both chromosome breakage and chromosome loss
    and hence can reflect exposure to agents with clastogenic or aneugenic modes of action.
    The use of MN as a measure of chromosomal damage has become a standard assay
    in both genetic toxicology testing and human biomonitoring studies and is described
    in Section 2.3.2.
    Sister chromatid exchanges (SCEs) are reciprocal DNA exchanges between the two
    sister chromatids of a duplicated chromosome and appear to be the consequence
    of DNA replication errors on a damaged template, possibly at the replication fork
    (for review see [5]). They are also considered to be associated with intrachromosomal
    homologous recombination repair, as induced by some metals [6]. Detection of SCEs
    is achieved by differential staining of the two sister chromatids after two rounds
    of replication in the presence of bromodeoxyuridine, the scoring being conducted in the
    second-division metaphase cells. Although sensitive in detecting DNA-toxicant
    interactions in PBLs of individuals exposed to some genotoxic carcinogens, SCEs are
    essentially biomarkers of exposure. They are not used so frequently anymore in human
    biomonitoring and genetic toxicology, due to their unclear mechanism of formation
    and uncertainty of their biological significance [5]. Moreover, Bonassi et al. [7] recently
    confirmed that they are not predictive for cancer risk. Therefore, the use of this
    endpoint as a measure of chromosomal damage is beyond the scope of this article
    and it will not be considered here.
    Original languageEnglish
    Title of host publicationBiomarkers of carcinogen exposure and early effects
    PublisherFarmer P. and Emeny J.
    Pages47-61
    Number of pages15
    Publication statusPublished - 2006

    Keywords

    • chromosome aberrations

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