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Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay

Abstract

To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between  More>>
Authors:
Gajski, Goran; [1]  Garaj-Vrhovac, Vera; [1]  Orescanin, Visnja [2] 
  1. Institute for Medical Research and Occupational Health, Mutagenesis Unit, 10000 Zagreb (Croatia)
  2. Ruder Boskovic Institute, 10000 Zagreb (Croatia)
Publication Date:
Aug 15, 2008
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 231; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2008.03.013; PII: S0041-008X(08)00145-2; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Subject:
60 APPLIED LIFE SCIENCES; DNA; DNA DAMAGES; IN VITRO; LYMPHOCYTES; OXIDATION; REGRESSION ANALYSIS
OSTI ID:
21140930
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; TXAPA9; TRN: US08R3512020442
Availability:
Available from http://dx.doi.org/10.1016/j.taap.2008.03.013;INIS
Submitting Site:
INIS
Size:
page(s) 85-93
Announcement Date:
Mar 20, 2009

Citation Formats

Gajski, Goran, Garaj-Vrhovac, Vera, and Orescanin, Visnja. Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay. United States: N. p., 2008. Web. doi:10.1016/j.taap.2008.03.013.
Gajski, Goran, Garaj-Vrhovac, Vera, & Orescanin, Visnja. Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay. United States. doi:10.1016/j.taap.2008.03.013.
Gajski, Goran, Garaj-Vrhovac, Vera, and Orescanin, Visnja. 2008. "Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay." United States. doi:10.1016/j.taap.2008.03.013. https://www.osti.gov/servlets/purl/10.1016/j.taap.2008.03.013.
@misc{etde_21140930,
title = {Cytogenetic status and oxidative DNA-damage induced by atorvastatin in human peripheral blood lymphocytes: Standard and Fpg-modified comet assay}
author = {Gajski, Goran, Garaj-Vrhovac, Vera, and Orescanin, Visnja}
abstractNote = {To investigate the genotoxic potential of atorvastatin on human lymphocytes in vitro standard comet assay was used in the evaluation of basal DNA damage and to investigate possible oxidative DNA damage produced by reactive oxygen species (ROS) Fpg-modified version of comet assay was also conducted. In addition to these techniques the new criteria for scoring micronucleus test were applied for more complete detection of baseline damage in binuclear lymphocytes exposed to atorvastatin 80 mg/day in different time periods by virtue of measuring the frequency of micronuclei, nucleoplasmic bridges and nuclear buds. All parameters obtained with the standard comet assay and Fpg-modified comet assay were significantly higher in the treated than in control lymphocytes. The Fpg-modified comet assay showed a significantly greater tail length, tail intensity, and tail moment in all treated lymphocytes than did the standard comet assay, which suggests that oxidative stress is likely to be responsible for DNA damage. DNA damage detected by the standard comet assay indicates that some other mechanism is also involved. In addition to the comet assay, a total number of micronuclei, nucleoplasmic bridges and nuclear buds were significantly higher in the exposed than in controlled lymphocytes. Regression analyses showed a positive correlation between the results obtained by the comet (Fpg-modified and standard) and micronucleus assay. Overall, the study demonstrated that atorvastatin in its highest dose is capable of producing damage on the level of DNA molecule and cell.}
doi = {10.1016/j.taap.2008.03.013}
journal = {Toxicology and Applied Pharmacology}
issue = {1}
volume = {231}
place = {United States}
year = {2008}
month = {Aug}
}