title: Commentary: critical questions, misconceptions and a road map for improving the use of the lymphocyte cytokinesis-block micronucleus assay for in vivo biomonitoring of human exposure to genotoxic chemicals-a HUMN project perspective.
abstract: The lymphocyte cytokinesis-block micronucleus (CBMN) assay has been applied in hundreds of in vivo biomonitoring studies of humans exposed to genotoxic chemicals because it allows the measurement of both structural and numerical chromosome aberrations. The CBMN cytome assay version which, apart from measuring micronuclei (MN) already present in cells in vivo or expressed ex vivo, also includes measurement of nucleoplasmic bridges (NPB), nuclear buds (NBUD), necrosis and apoptosis, is also increasingly being used in such studies. Because of the numerous published studies there is now a need to re-evaluate the use of MN and other biomarkers within the lymphocyte CBMN cytome assay as quantitative indicators of exposure to chemical genotoxins and the genetic hazard this may cause. This review has identified some important misconceptions as well as knowledge gaps that need to be addressed to make further progress in the proper application of this promising technique and enable its full potential to be realised. The HUMN project consortium recommends a three pronged approach to further improve the knowledge base and application of the lymphocyte CBMN cytome assay to measure DNA damage in humans exposed to chemical genotoxins: (i) a series of systematic reviews, one for each class of chemical genotoxins, of studies which have investigated the association of in vivo exposure in humans with MN, NPB and NBUD induction in lymphocytes; (ii) a comprehensive analysis of the literature to obtain new insights on the potential mechanisms by which different classes of chemicals may induce MN, NPB and NBUD in vitro and in vivo and (iii) investigation of the potential advantages of using the lymphocyte CBMN cytome assay in conjunction with other promising complementary DNA damage diagnostics to obtain an even more complete assessment of the DNA damage profile induced by in vivo exposure to chemical genotoxins in humans.
authors.affiliation: Laboratory of Cell Genetics, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussel, Belgium.
authors.forename: Micheline
authors.initials: M
authors.lastname: Kirsch-Volders
authors.affiliation: Unit of Clinical and Molecular Epidemiology, Area of Systems Approaches and Non-Communicable Diseases, IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.affiliation: Institute of Cancer Research, Medical University Vienna, Borschkegasse 8a, A-1090 Vienna, Austria.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Knasmueller
authors.affiliation: Children's Environmental Health Laboratory, School of Public Health Biorepository, University of California, Berkeley, CA, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Holland
authors.affiliation: Environmental Carcinogenesis Unit, IRCCS Azienda Ospedaliera Universitaria San Martino- IST Istituto Nazionale Ricerca sul Cancro, Largo Rosanna Benzi 10, Genova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Bolognesi
authors.affiliation: CSIRO Preventative Health Flagship, PO Box 10041, Adelaide BC 5000, Australia. Electronic address: michael.fenech@csiro.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Fenech
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D048749:Cytokinesis / Q000187:drug effects; D004249:DNA Damage; D004784:Environmental Monitoring; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective; D009153:Mutagens / Q000633:toxicity*
chemical_list: D009153:Mutagens
keywords: Biomonitoring; Chemical genotoxins; Cytokinesis-block; In vivo; Lymphocytes; Micronucleus