Genotoxic ability of cadmium, chromium and nickel salts studied by kinetochore staining in the cytokinesis-blocked micronucleus assay.
The aneugenic and clastogenic ability of cadmium chloride(II), cadmium sulfate(II), nickel chloride(II), nickel sulfate(II), chromium chloride(III) and potassium dichromate(IV) have been evaluated through kinetochore-stained micronucleus test. Traditional genotoxicity assays evaluate DNA damage, gene mutations and chromosome breakage. However, these tests are not adequate to detect aneugenic agents that do not act directly on DNA. Staining kinetochores in the cytokinesis-blocked micronucleus assay is a useful way to discriminate between clastogens and aneuploidogens and may allow a rapid identification of aneuploidy-inducing environmental compounds. Human diploid fibroblasts (MRC-5) were employed. All compounds increased micronuclei frequency in a statistically significant way. However, increases in kinetochore-positive micronuclei frequencies were higher than in kinetochore-negative ones. The present work demonstrates the genotoxic ability of the cadmium and chromium salts studied. Aneugenic as well as clastogenic ability could be observed with this assay. Nickel salts, as it was expected because of their known weak mutagenicity, showed lower genotoxic effects than the other metal salts studied. As the test employed only allows the detection of malsegregation, it is proposed that this mechanism is at least one of those by which the tested metal salts induced aneuploidy. On the other hand, visualization of kinetochores in all experiments suggests that the compounds studied did not act by damaging these structures.
Seoane
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Centro de Investigaciones en Genética Básica y Aplicada (CIGEBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, 60 y 118-CC. 296-B-1900 AVW, La Plata, Argentina.
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D000328:Adult; D019256:Cadmium Chloride / Q000633:toxicity*; D019187:Cadmium Compounds / Q000633:toxicity*; D002478:Cells, Cultured / Q000187:drug effects; D002712:Chlorides / Q000633:toxicity*; D017608:Chromium Compounds / Q000633:toxicity*; D020090:Chromosome Segregation / Q000187:drug effects; D002877:Chromosomes, Human / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006801:Humans; D018386:Kinetochores / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D015162:Micronucleus Tests; D009532:Nickel / Q000633:toxicity*; D011192:Potassium Dichromate / Q000633:toxicity*; D008941:Spindle Apparatus / Q000187:drug effects; D013431:Sulfates / Q000633:toxicity*
D019187:Cadmium Compounds; D002712:Chlorides; D017608:Chromium Compounds; D013431:Sulfates; C022838:nickel chloride; D009532:Nickel; C037123:cadmium sulfate; C017133:chromous chloride; D019256:Cadmium Chloride; D011192:Potassium Dichromate