scholarly journals Genotoxicity Assessment of Metal-Based Nanocomposites Applied in Drug Delivery

Materials ◽  
2021 ◽  
Vol 14 (21) ◽  
pp. 6551
Author(s):  
Sara Cardoso ◽  
Classius F. da Silva ◽  
Patrícia Severino ◽  
Amélia M. Silva ◽  
Selma B. Souto ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Comet Assay ◽  
Metal Nanoparticles ◽  
Size Range ◽  
Genetic Material ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Reliable Source ◽  
Nanometer Size Range ◽  
Dna Strand

Nanocomposites as drug delivery systems (e.g., metal nanoparticles) are being exploited for several applications in the biomedical field, from therapeutics to diagnostics. Green nanocomposites stand for nanoparticles of biocompatible, biodegradable and non-toxic profiles. When using metal nanoparticles for drug delivery, the question of how hazardous these “virus-sized particles” can be is posed, due to their nanometer size range with enhanced reactivity compared to their respective bulk counterparts. These structures exhibit a high risk of being internalized by cells and interacting with the genetic material, with the possibility of inducing DNA damage. The Comet Assay, or Single-Cell Gel Electrophoresis (SCGE), stands out for its capacity to detect DNA strand breaks in eukaryotic cells. It has huge potential in the genotoxicity assessment of nanoparticles and respective cells’ interactions. In this review, the Comet assay is described, discussing several examples of its application in the genotoxicity evaluation of nanoparticles commonly administered in a set of routes (oral, skin, inhaled, ocular and parenteral administration). In the nanoparticles boom era, where guidelines for their evaluation are still very limited, it is urgent to ensure their safety, alongside their quality and efficacy. Comet assay or SCGE can be considered an essential tool and a reliable source to achieve a better nanotoxicology assessment of metal nanoparticles used in drug delivery.

Detection of DNA strand breaks by comet assay in sputum leucocytes of bitumen-exposed workers: A pilot study

2010 ◽  
Vol 29 (9) ◽  
pp. 721-729 ◽  
Author(s):  
B. Marczynski ◽  
M. Raulf-Heimsoth ◽  
B. Pesch ◽  
B. Kendzia ◽  
HU Käfferlein ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Rank Correlation ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Blood Lymphocytes ◽  
Exposed Workers ◽  
Before And After ◽  
Dna Strand ◽  
Post Shift

DNA strand breaks were determined in leucocytes of induced sputum (IS) and compared with DNA strand breaks in blood lymphocytes from 42 bitumen-exposed workers pre and post shift. Comet assay results were expressed in arbitrary units based on visual scoring (sputum leucocytes) and Olive tail moment (OTM, blood lymphocytes). DNA damage in IS leucocytes was overall high but did not change during shift. Level of DNA strand breaks in IS samples correlated with total cell count and neutrophil content (Spearman rank correlation coefficient rs = 0.47, p = 0.001, rs= 0.48, p = 0.001, respectively) and with IL-8 concentration before and after shift (rs = 0.31, P = 0.048, and rs = 0.43, P = 0.005). DNA damage in IS was not associated with DNA strand breaks in blood lymphocytes (rs = —0.04, p = 0.802 before shift, rs = 0.27, p = 0.088 after shift). A higher level of DNA strand breaks was measured in blood lymphocytes before shift (median OTM 1.7 before and 1.3 after shift, p = 0.023). A strong correlation was found between the number of neutrophils and IL-8 concentration in IS before and after shift (rs = 0.77 and rs= 0.75, p < 0.001). This study showed an association between genotoxic and inflammatory effects in the lower airways and compared simultaneously DNA strand breaks in IS and blood of bitumen-exposed workers.

DNA strand breaks (comet assay) in blood lymphocytes from wild bottlenose dolphins

2013 ◽  
Vol 77 (1-2) ◽  
pp. 355-360 ◽  
Author(s):  
Richard F. Lee ◽  
Karrie Bulski ◽  
Jeffrey D. Adams ◽  
Margie Peden-Adams ◽  
Gregory D. Bossart ◽  
...  
Keyword(s):  
Comet Assay ◽  
Bottlenose Dolphins ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Blood Lymphocytes ◽  
Dna Strand

scholarly journals DNA damage in human whole blood caused by radiopharmaceuticals evaluated by the comet assay

Mutagenesis ◽  
2019 ◽  
Vol 34 (3) ◽  
pp. 239-244 ◽  
Author(s):  
Heinz H Schmeiser ◽  
Karl-Rudolf Muehlbauer ◽  
Walter Mier ◽  
Ann-Christin Baranski ◽  
Oliver Neels ◽  
...  
Keyword(s):  
Dna Damage ◽  
Comet Assay ◽  
Dna Strand Breaks ◽  
Strand Breaks ◽  
Human Whole Blood ◽  
Time Points ◽  
Dna Migration ◽  
Activity Concentrations ◽  
Positron Emitters ◽  
Dna Strand

Abstract Radiopharmaceuticals used for diagnosis or therapy induce DNA strand breaks, which may be detectable by single-cell gel electrophoresis (called comet assay). Blood was taken from patients before and at different time points after treatment with radiopharmaceuticals; blood cells were investigated by the comet assay using the percentage of DNA in the tail as the critical parameter. Whereas [225Ac]Ac-prostate-specific membrane antigen (PSMA)-617 alpha therapy showed no difference relative to the blood sample taken before treatment, beta therapy with [177Lu]Lu-PSMA-617 3 h post-injection revealed a small but significant increase in DNA strand breaks. In blood of patients who underwent positron emission tomography (PET) with either [18F]2-fluor-2-deoxy-D-glucose (FDG) or [68Ga]Ga-PSMA-11, an increase of DNA migration determined by the comet assay was not found when analysed at different time points (2–70 min) after intravenous tracer injection. Human whole blood was incubated with the targeted clinically relevant therapeutic radiopharmaceuticals [225Ac]Ac-PSMA-617, [177Lu]Lu-PSMA-617 and [90Y]Y-DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTA-TOC) at different activity concentrations (kBq/ml) for 5 days and then analysed by the comet assay. DNA damage increased with higher concentrations of all radiolabeled compounds tested. [177Lu]Lu-PSMA-617 caused higher blood cell radiotoxicity than equal activity concentrations of [90Y]Y-DOTA-TOC. Likewise, whole human blood was exposed to the positron emitters [18F]FDG and [68Ga]Ga-PSMA-11 in vitro for 24 h with activity concentrations ranging between 5 and 40 MBq/ml. The same activity concentration dependent elevated DNA migration was observed for both compounds although decay energies are different. This study demonstrated that the amount of DNA damage detected by the comet assay in whole human blood is similar among different positron emitters and divergent by a factor of 200 between alpha particles and beta radiation.

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