title: The in vivo or ex vivo origin of micronuclei measured in human biomonitoring studies.
abstract: The micronucleus test (MNT) is a well-established assay in genotoxicity testing and human biomonitoring. The cytokinesis-block micronucleus test (CBMNT) is the preferred method for measuring MN in cultured human lymphocytes from human subjects exposed to genotoxins. However, it is unclear to what extent mutagen exposure either leads to the formation of MN already in vivo or to the formation of MN ex vivo during cell culture as a consequence of persisting DNA damage. MN that were already induced in vivo can be determined by scoring MN in mononuclear lymphocytes 24 h after the start of the lymphocyte culture (i.e. in lymphocytes that did not divide yet). Results obtained for cancer patients after chemotherapy suggest that mutagen exposure in vivo mainly leads to the formation of MN during ex vivo proliferation of lymphocytes as a consequence of mis-repair of persistent damage. If these results also apply to other kinds of mutagen exposure, increased MN frequencies in the CBMNT can only be expected for exposures leading to a sufficient amount of damage that persists during ex vivo lymphocyte culture. For a better understanding of the origin of increased MN frequencies and the correct interpretation of results obtained with the CBMNT, further research is recommended: MN in mononuclear lymphocytes should be additionally scored 24 h after the start of the cultures, comparative investigation with the CBMNT and the MNT with reticulocytes should be performed and the kinetics of MN formation in lymphocyte cultures and the repair capacity of lymphocytes for different kinds of DNA damage should be characterised.
authors.affiliation: Institut für Humangenetik, Universität Ulm, D-89069 Ulm, Germany. guenter.speit@uni-ulm.de
authors.forename: Günter
authors.initials: G
authors.lastname: Speit
authors.forename: Jasmin
authors.initials: J
authors.lastname: Zeller
authors.forename: Simone
authors.initials: S
authors.lastname: Neuss
mesh_terms: D048749:Cytokinesis / Q000187:drug effects*; D004249:DNA Damage; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D008991:Monitoring, Physiologic / Q000379:methods; D009153:Mutagens / Q000633:toxicity*
chemical_list: D009153:Mutagens