engleski

Genotoxicity testing of therapeutical concentration of atorvastatin using the micronucleus test according to new scoring criteria

Although favorable results from a large number of controlled clinical trials underpin the benefits of atorvastatin therapy, it is not surprising that the safety of this drug has received much attention over the past few years regarding numerous side effects occuring in its highest therapeutical dose. In that context, goal of this research was assessment of the degree of DNA damage induced by highest therapeutical concentration of atorvastatin (80 mg/ml) in different time periods on human peripheral blood lymphocytes in vitro. For that purpose micronucleus test was used as a sensitive tool in detection of DNA malformations induced by these type of drug. In adition to the standard parameters such as number of micronuclei per binucleated cells, new criteria in scoring was applied measuring as well the incidence of nucleoplasmic bridges and nuclear buds to determine a wider range of genetic instabilities. The induction of micronuclei alone is considered to be an effective biomarker of processes associated with the DNA damage. Current evidence suggests that nucleoplasmic bridges derive from dicentric chromosomes and are therefore indicative of the DNA mis-repair, chromosome rearrangement or telomere end-fusion. Nuclear buds in another hand arise from the elimination of the amplified DNA and possibly from the elimination of the DNA-repair complexes which therefore may be considered a marker of gene amplification and altered gene dosage. In this respect, the micronucleus test represents an effective tool to be used with studies of cellular and nuclear dysfunctions caused by in vitro exposures to toxic substances. In our study all three parameters ; total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed lymphocytes than in controlled ones suggesting that atorvastatin caused alterations in cellular and nuclear structures under in vitro conditions.

atorvastatin; DNA damage; micronucleus test

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