Chromosomal damage

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.