Importance of detecting numerical versus structural chromosome aberrations

The Kidney Vero-E6 Cell Line: A Suitable Model to Study the Toxicity of Microcystins

“…Our data, together with those from other works, suggests that MCLR genotoxicity occurs indirectly by both clastogenic and aneugenic mechanisms: the first, possibly through oxidative stress; the second, perhaps through damages on the mitotic spindle, induced by the inhibition of PP1/PP2A. Since clastogenesis and aneugenesis have been associated with human cancer development [59] it can be hypothesized that both underlie the carcinogenic activity of MCLR. Moreover, the confirmation of genotoxic activity of MCLR in vivo is of major importance for regulatory purposes because a safe level could not be applied to clastogens conversely to aneugens [59,60].…”

“…Since clastogenesis and aneugenesis have been associated with human cancer development [59] it can be hypothesized that both underlie the carcinogenic activity of MCLR. Moreover, the confirmation of genotoxic activity of MCLR in vivo is of major importance for regulatory purposes because a safe level could not be applied to clastogens conversely to aneugens [59,60]. This is fundamental for the prevention of the risk of exposure of human populations to water contaminated with toxic cyanobacteria.…”

Centromere-localized breaks indicate the generation of DNA damage by the mitotic spindle

“…In such an event, a centromere-positive micronucleus is generated. Centromeres in micronuclei thus are reliable indicators of spindle defects, but more easily discernible than wrongly attached kinetochores (21,30). To confirm the origin of micronuclei in the Dido mutant, we labeled MEFs with antibodies to centromeres and α-tubulin, and studied these by fluorescence microscopy.…”

Presence of Dichlorodiphenyltrichloroethane (DDT) in Croatia and Evaluation of Its Genotoxicity

“…An increased number of micronucleated cells is a biomarker of genotoxic effects and can reflect exposure to agents with clastogenic modes of action (chromosome breaking; DNA as target) or aneugenic ones (aneuplodigenic; effect on chromosome number; mostly non-DNA target) (Albertini, 2000). The advantage of the CBMN assay is its ability to detect both clastogenic and aneugenic events, leading to structural and numerical chromosomal aberrations, respectively (Kirsch-Volders et al, 2002;Mateuca et al, 2006). Micronuclei observed in cultured lymphocytes are believed to arise primarily in vitro from: 1) chromatid-type chromosomal aberrations formed during DNA replication on a damaged template, 2) chromosome-type aberrations initiated before the mitosis and duplicated at replication, or 3) disturbances of mitotic apparatus leading to chromosome lagging.…”