Effects of cetirizine dihydrochloride on human lymphocytes in vitro: micronucleus induction. Evaluation of clastogenic and aneugenic potential using CREST and FISH assays.
Cetirizine dihydrocloride, a widely administered antiallergic drug with the amine piperazine in its molecule, was studied as to its ability to cause micronucleus formation in human lymphocyte cultures treated in vitro. Peripheral lymphocytes from four different donors were cultured and treated with different concentrations of the compound. Cetirizine dihydrocloride was shown to induce enhanced micronucleus frequency in a dose-dependent manner, although lymphocytes from the different donors showed different susceptibilities to the compound. The content of induced micronuclei was investigated in one of the four donors by two independent assays, CREST (the application of antikinetochore antibodies) and FISH (fluorescence in situ hybridization) on cytochalasin B-formed binucleated cells. It was shown that the induced micronuclei resulted from breakage events as well as chromosome loss, thus characterizing cetirizine dihydrocloride as both clastogen and aneugen. Since our results were derived only from in vitro experiments, we believe that an extensive in vivo study is necessary before drawing conclusions as to the effects of cetirizine dihydrochloride in patients.
Department of Biology, University of Patras, Greece.
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Vlastos
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Stephanou
D000328:Adult; D000782:Aneuploidy; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000473:pathology; D002503:Centromere / Q000187:drug effects / Q000235:genetics; D017332:Cetirizine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018386:Kinetochores / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015162:Micronucleus Tests; D016296:Mutagenesis / Q000187:drug effects / Q000235:genetics; D012044:Regression Analysis
D018926:Anti-Allergic Agents; D017332:Cetirizine