Inclusion of an extended treatment with recovery improves the results for the human peripheral blood lymphocyte micronucleus assay.

作者: James Whitwell , Robert Smith , Teresa Chirom , Gary Watters , Victoria Hargreaves

DOI: 10.1093/MUTAGE/GEZ011

关键词: MicronucleusCytarabineClastogenPhytohaemagglutininToxicityCytotoxicityMicronucleus testChemistryLymphocytePharmacology

摘要: The in vitro micronucleus (IVMN) test was endorsed for regulatory genotoxicity testing with adoption of the Organisation Economic Co-operation and Development (OECD) guideline (TG) 487 2010. This included two equally acceptable options extended treatment absence metabolic activation: a 1.5-2.0 cell cycles harvest at end (Option A) or followed by recovery prior to B). Although no preferences were discussed, TG cautions that Option B may not be appropriate stimulated lymphocytes where exponential growth declining 96 h after phytohaemagglutinin (PHA) stimulation. Following revision 2014 2016, emphasis has been placed on using A. Given purpose IVMN assay is determine both clastogenic aneugenic potential, authors believe compromised if an sensitive detection certain classes chemical. In this study, average generation time (via bromodeoxyuridine incorporation) human peripheral blood (HPBL) measured up 144 PHA addition, HPBL (MN) performed A schedules. Cytotoxicity (replication index) MN induction determined following 14 chemicals. data demonstrate actively divide beyond Furthermore, only observed some chemicals nucleoside analogues HPBLs period. For majority tested magnitude generally greater across wider concentration range schedule. steep concentration-related toxicity without more common, making selection suitable concentrations (within limits) analysis challenging.

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