scholarly journals Genotoxicity and cytotoxicity of sevoflurane in two human cell lines in vitro with ionizing radiation

2014 ◽  
pp. 104-109
Author(s):  
Miguel Alcaraz ◽  
Samuel Quesada ◽  
David Armero ◽  
Rocio Martín-Gil ◽  
Amparo Olivares ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
Human Lymphocytes ◽  
In Vitro Toxicity ◽  
X Rays ◽  
Normal Prostate ◽  
Cytotoxic Effects ◽  
Prostate Cells ◽  
Dose Dependent ◽  
Different Doses

Objective: To determine the in vitro toxicity of different concentrations of sevoflurane in cells exposed to X-ray. Methods: The genotoxic effects of sevofluorane were studied by means of the micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes. Subsequently, its cytotoxic effects on PNT2 (normal prostate) cells was determined using the cell viability test (MTT) and compared with those induced by different doses of X-rays. Results: A dose- and time-dependent cytotoxic effect of sevofluorane on PNT2 cells was determined (p> 0.001) and a dose-dependent genotoxic effect of sevofluorane was established (p> 0.001). Hovewer, at volumes lower than 30 μL of sevofluorane at 100%, a non-toxic effect on PNT2 cells was shown. Conclusion: Sevofluorane demonstrates a genotoxic capacity as determined in vitro by micronucleus test in cytokinesis-blocked cells of irradiated human lymphocytes.

In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests

2018 ◽  
Vol 21 (4) ◽  
pp. 262-270 ◽  
Author(s):  
Zehao Huang ◽  
Na Li ◽  
Kaifeng Rao ◽  
Cuiting Liu ◽  
Zijian Wang ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
A549 Cells ◽  
Quantitative Structure Activity Relationship ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Effects ◽  
Qsar Analysis ◽  
Cell Assays ◽  
Micronucleus Tests ◽  
Damaging Effects

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

Genotoxicity Studies on Sel-Plex®, a Standardized, Registered High-Selenium Yeast

2006 ◽  
Vol 25 (6) ◽  
pp. 477-485 ◽  
Author(s):  
James C. Griffiths ◽  
Ray A. Matulka ◽  
Ronan Power
Keyword(s):  
Chromosome Aberration ◽  
Micronucleus Test ◽  
Mutagenic Activity ◽  
Human Lymphocytes ◽  
Selenium Yeast ◽  
Yeast Saccharomyces Cerevisiae ◽  
Reverse Mutation ◽  
High Selenium ◽  
Chromosome Aberration Test

Selenium, recognized as an essential nutrient for human health, is a component of proteins and enzymes required for various biological functions and is currently being used as a feed supplement for livestock in geographical areas that are naturally low in selenium. Selenium is structurally similar to sulfur, replacing the sulfur atom in stoichiometric amounts and thus functions through an association with proteins, termed selenoproteins. In geographic areas low in selenium, there is the potential for animals (including humans) to become selenium deficient and this potential deficiency can be remedied by consumption of exogenous selenium, including selenium-enriched yeast ( Saccharomyces cerevisiae) that contains high levels of organic selenium (e.g., selenized yeast). A unique, standardized, registered high selenium food-grade baker’s yeast ( S. cerevisiae; Sel-Plex®), was tested in the following battery of Genotoxicity assays; (1) a bacterial reverse mutation test (Ames test); (2) an in vitro mammalian chromosome aberration test; and (3) a mouse micronucleus test. Under the conditions of this assay, Sel-Plex® showed no evidence of mutagenic activity in Salmonella typhimurium, in the bacterial reverse mutation test. Sel-Plex® did not induce significant chromosomal aberrations in cultured human lymphocytes in the in vitro mammalian chromosome aberration test. Sel-Plex® did not statistically increase the frequency or proportion of micronucleated immature erythrocytes in the mouse micronucleus test. Thus, from the studies presented here, the authors conclude that Sel-Plex® is nongenotoxic.

scholarly journals Evaluation of mutagenicity, genotoxicity and chronic toxicity of antiviral drug imidazolyl ethanamide pentandioic acid in in vitro and in vivo test systems

2021 ◽  
Vol 98 (5) ◽  
pp. 548-557
Author(s):  
E. A. Jain ◽  
D. Pleimes ◽  
A. A. Globenko
Keyword(s):  
Oral Administration ◽  
Chromosomal Aberrations ◽  
Ames Test ◽  
Chronic Toxicity ◽  
Micronucleus Test ◽  
Human Lymphocytes ◽  
Antiviral Drug ◽  
Systemic Exposure

Introduction. The antiviral properties of imidazolyl ethanamide pentandioic acid (IPA), the active compound of the drug product, has been proven in various experimental models. However, the literature data on the toxicological properties of IPA are limited.Purpose. To evaluate mutagenic and genotoxic properties in in vitro and in vivo models, as well as to study the toxicity of IPA following chronic oral administration to rats and dogs.Materials and methods. Mutagenic and genotoxic properties of IPA were assessed using the Ames test, the test of chromosomal aberrations in human lymphocytes, and the micronucleus test in rats. The chronic toxicity of IPA was studied in Sprague Dawley rats and beagle dogs of both sexes, to which IPA was administered orally at doses of 30-300 mg/kg/day for 26 and 39 weeks, respectively.Results and discussion. In the Ames test, the addition of IPA up to the maximum dose (5000 mcg/plate) did not result in the increase in the number of revertant colonies. At a concentration of up to 5000 mcg/ml, IPA did not cause chromosomal aberrations in human leukocytes. At doses doses ≤ 2000 mg/kg, IPA did not increase the amount of micronuclei in the bone marrow of rats. In chronic experiments, animals tolerated the administration of IPA well: the dose without an observed effect (NOEL) for rats and dogs was 300 mg/kg/day.Conclusion. IPA did not show mutagenic and genotoxic properties in standard in vitro and in vivo tests. With chronic oral administration to rats and dogs, NOEL IPA equal to 300 mg/kg/day provided a systemic exposure that was 8-10 and 41-65 times higher than that in humans, respectively. The results obtained allow us to consider the safety profile of the prolonged use in humans as favorable.

scholarly journals In vitro toxicity assessment of respirable solid surface composite sawing particles

2020 ◽  
Vol 36 (4) ◽  
pp. 250-262
Author(s):  
W Kyle Mandler ◽  
Seungkoo Kang ◽  
Mariana Farcas ◽  
Chaolong Qi ◽  
Sherri A Friend ◽  
...  
Keyword(s):  
Solid Surface ◽  
Geometric Mean ◽  
Construction Materials ◽  
Lavage Fluid ◽  
Cell Culture Supernatant ◽  
In Vitro Toxicity ◽  
Dependent Manner ◽  
Respirable Particles ◽  
Dose Dependent

Solid surface composites (SSCs) are a class of popular construction materials composed of aluminum trihydrate and acrylic polymers. Previous investigations have demonstrated that sawing SSC releases substantial airborne dusts, with a number-based geometric mean diameter of 1.05 µm. We reported that in mice, aspiration exposure to airborne SSC dusts induced symptoms of pulmonary inflammation at 24-h postexposure: neutrophilic influx, alveolitis, and increased lactate dehydrogenase (LDH) and pro-inflammatory cytokine levels in lavage fluid. The particles appeared to be poorly cleared, with 81% remaining at 14-day postexposure. The objective of this study was to determine the toxicity specifically of respirable particles on a model of human alveolar macrophages (THP-1). The relative toxicities of subfractions (0.07, 0.66, 1.58, 5.0, and 13.42 µm diameter) of the airborne particles were also determined. THP-1 macrophages were exposed for 24 h to respirable particles from sawing SSC (0, 12.5, 25, 50, or 100 µg/ml) or size-specific fractions (100 µg/ml). Exposure to respirable SSC particles induced THP-1 macrophage toxicity in a dose-dependent manner. Viability was decreased by 15% and 19% after exposure to 50 and 100 µg/ml SSC, respectively, which correlated with increased cell culture supernatant LDH activity by 40% and 70% when compared to control. Reactive oxygen species (ROS) production and inflammatory cytokines were increased in a dose-dependent manner. A size-dependent cytotoxic effect was observed in the cells exposed to subfractions of SSC particles. SSC particles of 0.07, 0.66, and 1.58 µm diameter killed 36%, 17%, and 22% of cells, respectively. These results indicate a potential for cytotoxicity of respirable SSC particles and a relationship between particle size and toxicity, with the smallest fractions appearing to exhibit the greatest toxicity.

scholarly journals Differential radiosensitivity of hypothalamo-pituitary function in the young adult rat

2001 ◽  
Vol 169 (3) ◽  
pp. 519-526 ◽  
Author(s):  
IC Robinson ◽  
KM Fairhall ◽  
JH Hendry ◽  
SM Shalet
Keyword(s):  
Cranial Irradiation ◽  
Male Rats ◽  
Pituitary Hormone ◽  
X Rays ◽  
Adult Rat ◽  
Reduced Body ◽  
Pituitary Glands ◽  
Dose Dependent ◽  
Endocrine Abnormality ◽  
Different Doses

Cranial irradiation in children and adults often results in irreversible hypopituitarism. The earliest and most common endocrine abnormality is GH deficiency, often followed by other pituitary hormone deficits. We investigated whether a similar pattern of progressive hypopituitarism could be reproduced in an animal model. Different doses of cranial irradiation were delivered to the hypothalamo-pituitary region of normal adult male rats, and the effects on their subsequent growth, pituitary weight and hormone contents were studied. Animals received cranial irradiation with 300 kV X-rays at doses of 0, 20, 22 or 24 Gy (n=15 per group) and five animals from each group were killed at 8, 14 or 20 weeks after irradiation. Their anterior pituitary glands were weighed and assayed for GH, LH, TSH, ACTH and prolactin (PRL) content. All three doses of irradiation reduced body weight compared with that in non-irradiated controls and compromised growth between 8 and 20 weeks. Pituitary weight increased between 8 and 20 weeks in control rats, whereas it decreased significantly in the irradiated animals. Irradiation induced time- and dose-dependent changes in pituitary hormone contents. GH and PRL were most sensitive and decreased by more than 90% after irradiation; TSH contents were unaffected 8 weeks after the lowest dose of irradiation, but were reduced at 14 and 20 weeks. LH and ACTH were the slowest to be affected, and only at the greater doses of radiation. Thus progressive multiple pituitary endocrine deficits can be induced differentially in rats by increasing doses of cranial irradiation. This model should prove useful for defining the sites and mechanisms by which cranial irradiation induces neuroendocrine dysfunction.

scholarly journals In vitro assessment of genotoxic and cytotoxic effects of Artemisia annua L. tincture

2021 ◽  
Vol 5 (2) ◽  
pp. 1
Author(s):  
Tamara Ćetković ◽  
Anja Haverić ◽  
Lejla Čaluk Klačar ◽  
Maida Hadžić Omanović ◽  
Sanin Haverić
Keyword(s):  
Peripheral Blood ◽  
Artemisia Annua ◽  
Neutral Red ◽  
Cytotoxic Effects ◽  
Artemisia Annua L ◽  
Peripheral Blood Culture ◽  
Pharmaceutical Form ◽  
In Series ◽  
Dose Dependent

The genus Artemisia (fam. Asteraceae) is one of the largest and widely distributed with around 500 species, majority used as aromatic and medicinal plants. Artemisia annua L. is widely used as a dietary spice, herbal tea, as a supplement, and in a non-pharmaceutical form for treatment of malaria and fever. It is orally consumed as capsules, extracts and tinctures and topically applied as an essential oil diluted in lotions and ointments. Artemisinin is the main constituent of Artemisia annua L. extracts. Since the discovery that the artemisinin is efficient in malaria treatment, there is also a growth in consumption of A. annua extracts for antitumour and even recently for antiviral treatments against SARS-CoV-2 infections. This study aimed to investigate genotoxic effect in peripheral blood culture and cytotoxic effects in cancer and normal cell lines, of commercially available A. annua L. tincture in series of dilutions. Both comet and neutral red uptake assays revealed dose-dependent genotoxicity and cytotoxicity of A. annua tincture dilutions. Comet assay revealed significantly increased DNA damage in peripheral blood cells while neutral-red assays showed increase in cytotoxicity (p<0.001) in both normal and cancer cell cultures treated with the lowest extract dilution compared to the highest one applied. Obtained results indicate caution needed in A. annua L. tincture use, especially when poorly diluted.

scholarly journals In Vitro Testing for Genotoxicity of Indigo Naturalis Assessed by Micronucleus Test

2010 ◽  
Vol 5 (7) ◽  
pp. 1934578X1000500
Author(s):  
Luca Dominici ◽  
Barbara Cerbone ◽  
Milena Villarini ◽  
Cristina Fatigoni ◽  
Massimo Moretti
Keyword(s):  
Micronucleus Test ◽  
Synthetic Dyes ◽  
Hepg2 Cell Line ◽  
Cytotoxic Effects ◽  
Natural Colorants ◽  
Cbmn Assay ◽  
Carcinogenic Agents ◽  
Indigo Naturalis ◽  
Indigofera Tinctoria

In the field of cosmetic dyes, used for coloring the hair and skin, there is a clear tendency to replace the widely used synthetic dyes by natural colorants, such as henna and mixtures of henna with indigo. The aim of this study was to estimate the genotoxicity of water and DMSO solutions of indigo naturalis (prepared from Indigofera tinctoria leaves) using the cytokinesis-blocked micronucleus (CBMN) assay in the human metabolically active HepG2 cell line. The cytotoxic effects of indigo solutions were first assessed by propidium iodide and fluorescein-diacetate simultaneous staining. For both solutions, cytotoxicity was always under 10%. Data obtained in the CBMN assay (for all concentrations tested) indicated that the frequency of MN (micronuclei) in exposed cells was no higher than the control. Both the water and DMSO solutions showed the same behavior. These results indicate that indigo naturalis exhibits neither cytotoxicity, nor genotoxicity for all concentrations tested, which may justify excluding indigofera and its components from the list of carcinogenic agents.

scholarly journals Activation effects of a prion protein fragment [PrP-(106-126)] on human leucocytes*

1996 ◽  
Vol 320 (2) ◽  
pp. 563-570 ◽  
Author(s):  
Luisa DIOMEDE ◽  
Silvano SOZZANI ◽  
Walter LUINI ◽  
Marina ALGERI ◽  
Luca DE GIOIA ◽  
...  
Keyword(s):  
Prion Protein ◽  
Human Lymphocytes ◽  
Cellular Prion Protein ◽  
Dependent Manner ◽  
Membrane Microviscosity ◽  
Peripheral Tissues ◽  
Cell Extracts ◽  
Dose Dependent ◽  
O2 Production

Prion-related encephalopathies are characterized by the intracerebral accumulation of an abnormal isoform of the cellular prion protein (PrPC) named scrapie prion protein (PrPSc). The pathological forms of this protein and its cellular precursor are not only expressed in the brain but also, at lower concentrations, in peripheral tissues. We recently showed that a synthetic peptide corresponding to residues 106–126 [PrP-(106–126)] of the human PrP is toxic to neurons and trophic to astrocytes in vitro. Our experiments were aimed at verifying whether PrP-(106–126) and other peptides corresponding to fragments of the amyloid protein purified from brains of patients with Gerstmann–Sträussler–Scheinker disease – namely PrP-(89–106), PrP-(106–114), PrP-(127–147) – were capable of stimulating circulating leucocytes. Native PrP expression in human lymphocytes, monocytes and neutrophils was first confirmed using PCR amplification of total RNA, after reverse transcription, and immunoblot analysis of cell extracts with anti-PrP antibodies. PrP-(106–126), but not the other peptides, increased membrane microviscosity, intracellular Ca2+ concentration and cell migration in circulating leucocytes, and O2-•production in monocytes and neutrophils. Membrane microviscosity was determined by the fluorescence polarization technique, using diphenylhexatriene as a probe, 300 s after the addition of PrP-(106–126) to the cell suspension in the concentration range 5–50 µM. The increase in intracellular Ca2+ elicited by PrP-(106–126) was dose-dependent in the range 5–500 µM. PrP-(106–126) stimulated O2-•production in monocytes and neutrophils in a dose- (10–300 µM) and time-(5–30 min) dependent manner in the presence of 10 µM dihydrocytochalasin B. Both the increase in Ca2+ concentration and the O2-•production were partially sensitive to pertussis toxin. PrP-(106–126) stimulated leucocyte migration in a dose-dependent (30–300 µM) manner and, at the highest concentration used, this migration was comparable with that elicited by 2.5 nM interleukin 8 or 10 nM fMet-Leu-Phe peptide.

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