scholarly journals Cytotoxic, clastogenic and genotoxic effects of cis-tetraammine(oxalato)ruthenium(III) dithionate on human peripheral blood lymphocytes

2020 ◽  
Vol 42 ◽  
pp. e50517
Author(s):  
Manuela da Rocha Matos Rezende ◽  
Vivianne de Souza Velozo-Sá ◽  
Cesar Augusto Sam Tiago Vilanova-Costa ◽  
Elisangela Silveira-Lacerda

There is a concern about stablishing the clinical risk of drugs used for cancer treatment. In this study, the cytotoxic, clastogenic and genotoxic properties of cis-tetraammine(oxalato)ruthenium(III) dithionite - cis-[Ru(C2O4)(NH3)4]2(S2O6), were evaluated in vitro in human lymphocytes. The mitotic index (MI), chromosomal aberrations (CA) and DNA damage by comet assay were also analyzed. The MTT test revealed that the ruthenium compound showed a slight cytotoxic effect at the highest concentration tested. The IC50 value for the compound after 24 hours of exposure was 185.4 µM. The MI values of human peripheral blood lymphocytes treated with 0.015, 0.15, 1.5 and 150 µM of cis-[Ru(C2O4)(NH3)4]2(S2O6) were 6.1, 3.9, 3.2 and 0.2%, respectively. The lowest concentration, 0.015 µM, did not show any cytotoxic activity. The CA values for the 0.015, 0.15 and 1.5 µM concentrations presented low frequency (1.5, 1.6 and 2.3%, respectively), and did not express clastogenic activity when compared to the negative control, although it was observed clastogenic activity in the highest concentration tested (150 µM). The results obtained by the comet assay suggest that this compound does not present genotoxic activity at lower concentrations. The results show that cis-[Ru(C2O4)(NH3)4]2(S2O6) has no cytotoxic, clastogenic or genotoxic in vitro effects at concentrations less than or equal to 0.015 µM. This information proves as promising in the treatment of cancer and is crucial for future trials.

2015 ◽  
Vol 66 (2) ◽  
pp. 153-158 ◽  
Author(s):  
Fulya Dilek Gökalp Muranli ◽  
Martin Kanev ◽  
Kezban Ozdemir

Abstract The aim of this study was to evaluate the genetic damage in human peripheral blood lymphocytes following 24 and 48- hour exposure to a commercial diazinon formulation Basudin 60EM® at concentrations between 0.01 and 40 μg mL-1. For this purpose we used the micronucleus (MN), fluorescence in situ hybridization (FISH), and alkaline single cell gel electrophoresis (comet) assay. Diazinon significantly increased the frequency of micronucleated cells compared to control. Forty-eight-hour exposure increased this frequency even at lower concentrations (0.01-10 μg mL-1). The FISH results revealed aneugenic effects at 10 μg mL-1. The comet assay also confirmed DNA damage at concentrations between 10 and 40 μg mL-1. Our findings have confirmed the genotoxic potential of diazinon and its cytotoxic effect on human lymphocytes. The increased DNA damage in our study raises concern about the current assessment of the health risk posed by this pesticide and calls for a high level of caution in agricultural and household use.


2017 ◽  
Vol 68 (4) ◽  
pp. 322-335 ◽  
Author(s):  
Karlo Jurica ◽  
Irena Brčić Karačonji ◽  
Vesna Benković ◽  
Nevenka Kopjar

Abstract This study investigated the mechanisms of hydroquinone toxicity and assessed the relationships between its cytotoxic, genotoxic, and cytogenetic effects tested at 8, 140, and 280 μg mL-1 in human peripheral blood lymphocytes exposed for 24 h. The outcomes of the treatments were evaluated using the apoptosis/necrosis assay, the alkaline comet assay, and the cytokinesis-block micronucleus (CBMN) cytome assay. The tested hydroquinone concentrations produced relatively weak cytotoxicity in resting lymphocytes, which mostly died via apoptosis. Hydroquinone’s marked genotoxic effects were detected using the alkaline comet assay. Significantly decreased values of all comet parameters compared to controls indicated specific mechanisms of hydroquinone-DNA interactions. Our results suggest that the two higher hydroquinone concentrations possibly led to cross-linking and adduct formation. Increased levels of DNA breakage measured following exposure to the lowest concentration suggested mechanisms related to oxidative stress and inhibition of topoisomerase II. At 8 μg mL-1, hydroquinone did not significantly affect MN formation. At 140 and 280 μg mL-1, it completely blocked lymphocyte division. The two latter concentrations also led to erythrocyte stabilization and prevented their lysis. At least two facts contribute to this study’s relevance: (I) this is the first study that quantifies the degree of reduction in total comet area measured in lymphocyte DNA after hydroquinone treatment, (II) it is also the first one on a lymphocyte model that adopted the “cytome” protocol in an MN assay and found that lymphocytes exposure even to low hydroquinone concentration resulted in a significant increase of nuclear bud frequency. Considering the limitations of the lymphocyte model, which does not possess intrinsic metabolic activation, in order to unequivocally prove the obtained results further studies using other appropriate cell lines are advised.


2017 ◽  
Vol 33 (12) ◽  
pp. 938-945 ◽  
Author(s):  
Cynthia Paz-Trejo ◽  
Sandra Gómez-Arroyo

This study aims to evaluate the genotoxic potential of four commercial pesticides with diverse health categorizations by different world associations currently in use. We tested the fungicide mancozeb and the insecticides pirimicarb, monocrotophos and permethrin. The research was done with in vitro human peripheral blood lymphocytes using the DNA single gel electrophoresis assay and the cytokinesis-block micronucleus (MN) test, where we analysed common parameters such as the tail moment and the frequency of MN formation. We also measured other parameters like frequency of nucleoplasmic bridges, nuclear buds, apoptosis and necrosis with the MN test. Each pesticide induced significant differences in all of these parameters when compared with the negative control and showed different behaviours in the concentration-dependent response. This could be attributed to their genotoxic potential where mancozeb and monocrotophos induced the highest genetic damage, permethrin caused mainly cell death and pirimicarb had the least impact upon cells. This research provides valuable data about the harmful effects of these pesticides on human cells and may be an important contribution in the construction of a unique international classification of health and to reinforce the use of genotoxic analyses to regulate the use of pesticides.


2018 ◽  
Vol 34 (5) ◽  
pp. 293-300 ◽  
Author(s):  
Serpil Könen-Adıgüzel ◽  
Serap Ergene

Engineered nanoparticles (ENPs) are used in a wide range of applications because of their unique properties. Cerium dioxide nanoparticles (CeO2 NPs) are one of the important ENPs, and they can cause negative health effects, such as genotoxicity, in humans and other living organisms. The aim of this work was to analyze the genotoxic effects of short-term (3–24 h) CeO2 NPs exposure to cultured human blood lymphocytes. Three genotoxicity systems “cytokinesis-block micronucleus test, comet assay, and gamma H2AX test” were used to show the genotoxic potential of CeO2 NPs (particle size <25 nm, concentrations: 6, 12, and 18 µg/mL). Hydrogen peroxide was selected as the positive-control genotoxic agent. Our results indicate that CeO2 NPs have genotoxic potential on human peripheral blood lymphocytes cells even at 3–24 h exposure under in vitro conditions.


1989 ◽  
Vol 8 (5) ◽  
pp. 349-353 ◽  
Author(s):  
B.B. Ghosh ◽  
G. Talukder ◽  
A. Sharma

Trimethyltin chloride was found to induce cytotoxic damage in vitro in human peripheral blood lymphocytes. Two concentrations (0.5 μg and 1.0 μg) were added to lymphocytes from male and female subjects in mitogen stimulated and serum supplemented culture medium for 72 h. A dose-related increase of inhibition of replication index (P < 0.01) and cell division (P < 0.001) was observed. The frequencies of abnormal cells and chromosomal aberrations such as chromatid and chromosome breaks, dicentrics, triradial and quadriradial configurations were increased significantly (P < 0.001), as were micronucleus counts (P < 0.001) and sister chromatid exchanges (P < 0.001). Endoreduplication, an extremely rare spontaneous event in human lymphocytes, was observed in a few cases at all dose levels. The effects were more pronounced in lymphocytes obtained from habitual smokers.


Sign in / Sign up

Export Citation Format

Share Document