PMID- 30264469 OWN - NLM STAT- MEDLINE DCOM- 20190214 LR - 20190215 IS - 1098-2280 (Electronic) IS - 0893-6692 (Linking) VI - 60 IP - 1 DP - 2019 Jan TI - Chromosome Missegregation and Aneuploidy Induction in Human Peripheral Blood Lymphocytes In vitro by Low Concentrations of Chlorpyrifos, Imidacloprid and alpha-Cypermethrin. PG - 72-84 LID - 10.1002/em.22235 [doi] AB - Chlorpyrifos, imidacloprid, and alpha-cypermethrin are some of the most widely used insecticides in contemporary agriculture. However, their low-dose, nontarget genotoxic effects have not been extensively assayed. As one of the most relevant cancer biomarkers, we aimed to assess the aneuploidy due to chromosome missegregation during mitosis. To aim it we treated human lymphocytes in vitro with three concentrations of insecticides equivalents relevant for real scenario exposure assessed by regulatory agencies. We focused on chlorpyrifos as conventional and imidacloprid and alpha-cypermethrin as sustainable use insecticides. Cytokinesis-blocked micronucleus assay was performed coupled with fluorescence in situ hybridization (FISH) with directly labeled pancentromeric probes for chromosomes 9, 18, X and Y. None of the insecticides induced significant secondary DNA damage in terms of micronuclei (MN), nuclear buds (NB), or nucleoplasmic bridges (NPB). However, significant disbalances in chromosomes 9, 18, X and Y, and in insecticide-treated cells has been observed. According to recent studies, these disbalances in chromosome numbers may be atributted to defect sister chromatid cohesion which contribute to the increase of chromosome missegregation but not to micronuclei incidence. We conclude that tested insecticidal active substances exert chromosome missegregation effects at low concentrations, possibly by mechanism of sister chromatid cohesion. These findings may contribute to future risk assesments and understanding of insecticide mode of action on human genome. Environ. Mol. Mutagen. 60:72-84, 2019. (c) 2018 Wiley Periodicals, Inc. CI - (c) 2018 Wiley Periodicals, Inc. FAU - Muzinic, Vedran AU - Muzinic V AD - Unit of Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia. FAU - Ramic, Snjezana AU - Ramic S AD - Department of Oncological Pathology, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia. FAU - Zeljezic, Davor AU - Zeljezic D AD - Unit of Mutagenesis, Institute for Medical Research and Occupational Health, Zagreb, Croatia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180927 PL - United States TA - Environ Mol Mutagen JT - Environmental and molecular mutagenesis JID - 8800109 RN - 0 (Insecticides) RN - 0 (Neonicotinoids) RN - 0 (Nitro Compounds) RN - 0 (Pyrethrins) RN - 1TR49121NP (cypermethrin) RN - 3BN7M937V8 (imidacloprid) RN - JCS58I644W (Chlorpyrifos) SB - IM MH - *Aneuploidy MH - Chlorpyrifos/*toxicity MH - Chromosome Aberrations/*chemically induced MH - Chromosome Segregation/*drug effects/genetics MH - Chromosomes, Human, Pair 18/drug effects MH - Chromosomes, Human, Pair 9/drug effects MH - Chromosomes, Human, X/drug effects MH - Chromosomes, Human, Y/drug effects MH - DNA Damage/*drug effects MH - Humans MH - In Situ Hybridization, Fluorescence MH - Insecticides/*toxicity MH - Lymphocytes/drug effects MH - Micronucleus Tests MH - Neonicotinoids/*toxicity MH - Nitro Compounds/*toxicity MH - Pyrethrins/*toxicity OTO - NOTNLM OT - Chlorpyrifos OT - aneuploidy OT - fluorescence in situ hybridization OT - genotoxicity OT - imidacloprid OT - alpha-cypermethrin EDAT- 2018/09/29 06:00 MHDA- 2019/02/15 06:00 CRDT- 2018/09/29 06:00 PHST- 2018/04/04 00:00 [received] PHST- 2018/07/05 00:00 [revised] PHST- 2018/07/12 00:00 [accepted] PHST- 2018/09/29 06:00 [pubmed] PHST- 2019/02/15 06:00 [medline] PHST- 2018/09/29 06:00 [entrez] AID - 10.1002/em.22235 [doi] PST - ppublish SO - Environ Mol Mutagen. 2019 Jan;60(1):72-84. doi: 10.1002/em.22235. Epub 2018 Sep 27.