Genotoxicity of all-trans retinoic acid (ATRA) and its steroidal analogue EA-4 in human lymphocytes and mouse cells in vitro

DNA fragmentation induced by all‐trans retinoic acid and its steroidal analogue EA‐4 in C2C12 mouse and HL‐60 human leukemic cells in vitro

“…In a recent publication, fluorescence in situ hybridization and CREST analysis in human lymphocytes and C 2 C 12 mouse cells, respectively, revealed that ATRA and EA‐4 induce chromosome fragmentation through micronucleation (Alakhras et al ., ). However, at high concentration (10 –4 M) a mild effect on chromosome delay is noticed.…”

“…After DNA damage, checkpoint arrest allows additional time for repair before cell cycle progression and it can prevent proliferation of severely damaged cells permanently (Jeggo and Lobrich, 2006). Indeed, as it was recently referred, ATRA and EA-4 induced DNA damage and perturbations in cell cycle progression of C 2 C 12 cells, indicating that DNA repair is not completely functional (Alakhras et al, 2011). The cellular response to DNA damaging agents (e.g.…”

“…Centrosome amplification and multipolarity can lead to mis-segregation of chromosomes, which develop aneuploidy (Fletcher and Muschel, 2006). Actually, chromosome fragmentation and centrosome amplification were observed after treating C 2 C 12 mouse cells with ATRA and EA-4, resulting in genetic instability that leads to aneuploidy (Alakhras et al, 2011).…”

“…Recently, it was observed that ATRA and its analogue EA-4 are cytotoxic and genotoxic to human lymphocytes and C 2 C 12 mouse cells because they reduce cellular proliferation rate and induce micronucleation in both cell systems (Alakhras et al, 2011). Micronucleation is mainly generated via chromosome breakage and to a lesser extent via chromosome delay.…”

“…Analysis of the mitotic spindle in mouse cells has shown that they affect chromosome orientation during metaphase and induce centrosome defects as well as microtubule arrays disruption in interphase cells. Furthermore, ATRA and EA-4 affect mitotic progression by accumulation of cells in anaphase and telophase with various abnormal figures such as micronucleus inclusion, multiple signals of γ-tubulin, nucleoplasmic bridges and multinucleation (Alakhras et al, 2011).…”