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

• Published in: Cancer letters Vol. 306; no. 1; pp. 15 - 26
• Main Authors: Alakhras, Raghda S, Stephanou, Georgia, Demopoulos, Nikos A, Nikolaropoulos, Sotiris S
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.07.2011
• Subjects: Animals; ATRA-Retinoids; Cell Cycle; Cell Nucleus - metabolism; Centrosome - ultrastructure; Chromosome breakage; Chromosome delay; chromosomes; Chromosomes - ultrastructure; DNA Damage; fluorescent antibody technique; genotoxicity; Hematology, Oncology and Palliative Medicine; Humans; In Vitro Techniques; interphase; lymphocytes; Lymphocytes - drug effects; Lymphocytes - metabolism; Mice; Micronucleation; Microscopy, Fluorescence - methods; Microtubules - ultrastructure; Mitosis; Mitotic spindle defect; Multinucleation; Mutagens; retinoic acid; Spindle Apparatus; Steroids - pharmacology; Tretinoin - analogs & derivatives; Tretinoin - pharmacology; Chromosome delay; Mitotic spindle defect; Multinucleation; Chromosome breakage; Micronucleation; ATRA-Retinoids
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2011.02.010

Abstract The aim of our study is to: (a) investigate whether ATRA and its steroidal analogue EA-4 enhance micronucleation in human lymphocytes and mouse cells in vitro and 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.