Cytogenetic Methods in Human Biomonitoring: Principles and Uses

Abstract

Cellular phenotypes can be applied as biomarkers to differentiate normal from abnormal biological -conditions. Several cytogenetic methods have been developed and allow the accurate detection of such phenotypic changes.Based on their mechanisms of formation, cellular phenotypes may be used either as biomarkers of exposure or as biomarkers of effect. Therefore, it is important that cytogenetic methods implemented in human biomonitoring should be based on a good knowledge of these mechanisms.In this chapter, we aim to review the mechanistic basis, the methodology, and the use in human biomonitoring studies of four major cytogenetic endpoints: sister chromatid exchanges (SCEs), high frequency cells (HFCs), chromosomal aberrations (CAs), and micronuclei (MN). In addition, an overview of potential confounding factors on the induction of these cytogenetic makers is presented. Furthermore, the combination of cytogenetics with molecular methods, which allows chromosome and gene identification on metaphase as well as in interphase cells with high resolution, is discussed. Finally, practical recommendations for an efficient application of these cytogenetic assays and a correct interpretation of the results on the basis of cellular phenotype(s) assessment in human biomonitoring are highlighted.

Genotoxicity assessment in iron deficiency anemia patients using sister chromatid exchanges and chromosomal aberrations assays

“…However, it is agreed that SCEs are initiated by the collapse of a replication fork when it encounters a break in one parental strand. Repair of the stalled fork is mediated by a homologous recombination pathway that might result in SCEs [41]. In addition, previous studies have suggested a lack of association between SCEs and cancer prediction [30].…”

“…It is notable that neither the clinical significance nor the mechanisms that lead to the formation of SCEs are understood [41]. However, it is agreed that SCEs are initiated by the collapse of a replication fork when it encounters a break in one parental strand.…”

Genotoxic Evaluation of Duloxetine II. The Effect on the Number of Sister Chromatid Exchanges, the Mitotic Index, and the Proliferation Kinetics in Mouse Bone Marrow

“…19) The biomarker has been widely used to detect chromosome instability potential for a variety of xenobiotics in both in vitro and in vivo experimental models, as well as to evaluate the genotoxic effect caused by exposure to industrial, environmental, cosmetic or pharmaceutical agents, among others. 20,21) In regard to carcinogenesis, the induction of SCE has been considered of lower relevance, however, it is pertinent to mention that in diseases such as Bloom syndrome and Fanconi anemia spontaneous or induced SCE are usually found in excess, and that both conditions are prone to develop cancer; moreover, in other types of cancer SCE has been a useful biomarker, for example, in familial breast cancer patients. 22) In the case of antidepressants the assay has also been successfully applied.…”

DNA excision repair and double-strand break repair gene polymorphisms and the level of chromosome aberration in children with long-term exposure to radon

“…These disturbances lead to cell death, apoptosis and malignant transformation. CA reflect an individual's susceptibility to a complex of endogenous and exogenous factors and can be markers of genotoxic risk (Mateuca et al 2012;Vodenkova et al 2015). Significant research indicates that cytogenetic indicators are useful biomarkers for genotoxic and carcinogenic responses (including the influence of radiation) in occupational and domestic conditions (Norppa 2004).…”