Genotoxicity evaluation of HMG CoA reductase inhibitor rosuvastatin.
The genotoxic potential of rosuvastatin as one of the statin drugs was assessed by chromosomal aberrations (CAs), micronucleus (MN) and DNA damage by comet assay in the human peripheral blood lymphocytes. Rosuvastatin was used at concentrations of 0.0625, 0.125, 0.25, 0.5 and 1 µg/mL for these in vitro assays. In all assays, a negative and positive control were also included. CA frequencies were significantly increased in all concentrations at 24 hours and significantly increased in all concentrations except 0.0625 µg/mL at 48 hours, compared to the negative control. Rosuvastatin has a decreased mitotic index (MI) at 0.5- and 1-µg/mL concentrations at 24 hours and at 0.25, 0.5 and 1 µg/mL at 48 hours. A significant increase was observed for induction of MN in all treatments, compared to the negative control. Cytokinesis-block proliferation indices were not affected by treatments with rosuvastatin. In the comet assay, significant increases in comet tail length and tail moment were observed at 0.0625-, 0.5- and 1-µg/mL concentrations. Comet intensity was significantly increased in all concentrations except 0.0625 µg/mL. According to these results, rosuvastatin is cytotoxic and clastogenic/aneugenic in human peripheral lymphocytes. Further studies should be conducted in other test systems to evaluate the full genotoxic potential of rosuvastatin.
Department of Biology, Faculty of Art and Sciences, Sakarya University , Sakarya , Turkey and.
Ahmet Ali
AA
Berber
Mustafa
M
Celik
Hüseyin
H
Aksoy
D002869:Chromosome Aberrations / Q000139:chemically induced; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000633:toxicity*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D008214:Lymphocytes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D015162:Micronucleus Tests; D008940:Mitotic Index; D011743:Pyrimidines / Q000008:administration & dosage / Q000633:toxicity*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium
Chromosomal aberrations; comet assay; genotoxicity; human blood lymphocytes; micronuclei; rosuvastatin; statin