Document Detail


Genotoxicity testing of PLGA-PEO nanoparticles in TK6 cells by means of the comet assay and the cytokinesis-block micronucleus assay.
MedLine Citation:
PMID:  22814198     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The in vitro genotoxicity of PLGA-PEO (poly-lactic-co-glycolic acid-polyethylene oxide copolymer) nanoparticles was assessed in TK6 cells using the comet assay as well as cytokinesis- block micronucleus (CBMN) assay. The cells were exposed to 0.12-75μg/cm(2) of PLGA-PEO nanoparticles during 2 and 24hours for analysis in the comet assay, and to 3-75μg/cm(2) of these nanoparticles during 4, 24, 48 and 72hours, respectively, for analysis in the CBMN assay. Two different protocols for treatment with cytochalasin B were used. We found that PLGA-PEO was neither cytotoxic (measured by relative cell growth and cytokinesis-block proliferation index, CBPI), nor did it induce DNA strand-breaks (detected by the comet assay) or oxidative DNA lesions (measured by the comet assay combined with the use of the lesion-specific enzyme formamidopyrimidine-DNA-glycosylase). There were no statistically significant differences in the frequencies of micro-nucleated bi-nucleated cells (MNBNCs) between untreated and treated cells in either of the conditions used. This suggests that PLGA-PEO did not have potential genotoxicity. However, in two experimental protocols of the micronucleus assay, PLGA-PEO nanoparticles showed a weak but significant increase in the level of MN in mono-nucleated cells, viz. in cells treated for 48h with PLGA-PEO nanoparticles when cytochalasin B was added for the last 24h (1(st) protocol), and in cells treated for 24h with PLGA-PEO nanoparticles followed by removal of the latter and addition of cytochalasin B for another 24h afterwards (2(nd) protocol). It remains unclear whether the increase of MNMNC after treatment with PLGA-PEO nanoparticles is the effect of a possible, weak aneugenic potential or early effect of these particles, or due to another reason. These results suggest that aneugenicity in addition to clastogenicity may be considered as an important biomarker when assessing the genotoxic potential of polymeric nanoparticles.
Authors:
Kazimirova Alena; Magdolenova Zuzana; Barancokova Magdalena; Staruchova Marta; Volkovova Katarina; Dusinska Maria
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-16
Journal Detail:
Title:  Mutation research     Volume:  -     ISSN:  0027-5107     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Slovak Medical University, Limbova 14, 83303 Bratislava, Slovakia.
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