Molecular mechanisms by which in vivo exposure to exogenous chemical genotoxic agents can lead to micronucleus formation in lymphocytes in vivo and ex vivo in humans

Publication date: Available online 7 June 2016 Source:Mutation Research/Reviews in Mutation Research Author(s): Michael Fenech, Siegfried Knasmueller, Claudia Bolognesi, Stefano Bonassi, Nina Holland, Lucia Migliore, Fabrizio Palitti, Adayapalam T. Natarajan, Micheline Kirsch-Volders The purpose of this review is to summarise current knowledge on the molecular mechanisms by which in vivo exposure to exogenous chemical genotoxins in humans induces micronuclei (MNi) and other nuclear anomalies in lymphocytes in vivo and ex vivo after nuclear division in vitro. MNi originate from acentric chromosome fragments and/or whole chromosomes that are unable to engage with the mitotic spindle and/or fail to segregate properly to the daughter nuclei during anaphase. The lagging fragments or whole chromosomes are surrounded by membrane and become MNi. Acentric fragments are caused by failure of repair or mis-repair of DNA strand breaks which may be induced by chemicals that (i) damage the phosphodiester backbone of DNA, and/or (ii) inhibit the DNA damage response mechanisms or repair of DNA strand breaks and/or (iii) cause DNA replication stress due to DNA adduct or cross-link formation. MNi originating from lagging whole chromosomes may be induced by chemicals that cause defects in centromeres or the mitotic machinery. Mis-repair of chemically-induced DNA breaks may also cause formation of dicentric chromosomes and nucleoplasmic bridges (NPBs) between daughter nuclei...
Source: Mutation Research Reviews in Mutation Research - Category: Genetics & Stem Cells Source Type: research