Genotoxicity of all-transretinoic acid (ATRA) and its steroidal analogue EA-4 in human lymphocytes and mouse cellsin vitro

The aim of our study is to: (a) investigate whether ATRA and its steroidal analogue EA-4 enhance micronucleation in human lymphocytes and mouse cellsin vitroand clarify the micronucleation mechanism by FISH and CREST analysis respectively, and (b) analyze their effect on spindle organization by immunofluorescence of β- and γ-tubulin in mouse cells. We found that they: (a) induce micronucleation mainly via chromosome breakage and chromosome delay in a lesser extent, (b) disturb microtubule network, chromosome orientation and centrosome duplication/separation, (c) accumulate cell cycle at ana-telophases, which exert micronucleation, multiple γ-tubulin signals, nucleoplasmic bridges and multinucleation, and (d) generate multinucleated and multimicronucleated interphase cells.