Genotoxic evaluation of the furylethylene derivative 2-furyl-1-nitroethene in cultured human lymphocytes

Borroto, Jorge I. González; Creus, A.; Marcos, Ricard

doi:10.1016/s1383-5718(01)00262-5

Cited by 19 publications

(8 citation statements)

References 22 publications

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“…The MN assay is generally used to determine the in vivo genotoxicity of carcinogens in normal cells like human hymphocytes (Gonzalez Borroto et al, 2001;Migliore et al, 2002). Only a few recent publications reported MN formation in cell lines derived from tumours (Truter et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour

et al. 2003

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Apoptosis induction and micronuclei formation were compared following cytotoxic treatments in two rat glioma differing in p53 integrity. In vitro, micronuclei emergence but not apoptosis was linked to the p53 mutated status. In vivo, micronuclei assays were more sensitive to evaluate DNA damage induced by chemotherapy in a p53-mutated solid tumour. (Mow et al, 2001). The product of the tumour-suppressor gene p53 is a key mediator in this process (Soussi, 2000). In normal cells, wild-type p53 either arrests cell proliferation until the genetic damage is repaired or forces the cell to commit apoptosis (Cadwell and Zambetti, 2001). In cancer cells, where p53 alleles are often mutated, decrease in apoptosis can be compensated by the process of mitotic catastrophe, a form of cell death resulting from abnormal mitosis and leading to the formation of cells with multiple micronuclei (MN) (Roninson et al, 2001). This study aimed to compare induction of apoptosis and MN formation after chemo-or radiotherapy, in vitro in two rat glioma cell lines differing in p53 integrity, the 9L expressing a mutated p53 gene and the C6 the wild-type gene, and in vivo on established 9L solid tumours. MATERIALS AND METHODS Animals and cell linesAll experiments on Fischer 344 rats have been carried out with local ethical committee approval and met the standards required by the UKCCCR guidelines (Workman et al, 1998). The 9L gliosarcoma cell line and the C6 glioblastoma cell line were maintained in complete medium, RPMI 1640 supplemented with 10% foetal calf serum, 1% L-glutamine, 1% sodium pyruvate, 1% nonessential amino acids, 100 IU ml À1 penicillin and 100 mg ml À1 streptomycin. In vitro and in vivo radio-or chemotherapyFor in vitro treatments, 9L and C6 cells were g-irradiated (80 Gy, 137 Cs irradiator) or treated for 2 h with chemotherapeutic drugs and recultured during 24 or 72 h for apoptosis tests or 4 h for MN assays. For in vivo treatments, tumour-bearing rats (10 5 9L s.c. at day 0) received i.p. injections of cisplatin (1 mg kg À1 ), or were irradiated locally at the tumour site (20 Gy) at days 4, 11 and 18 and were killed the day after. The tumours were then dissected and prepared distinctly for apoptosis or MN assays. Apoptosis assaysAnalysis of caspase 3 activity Caspase-3 activation was measured in vitro by the cleavage of a specific fluorogenic substrate (Ac-DEVD-AMC, BD Biosciences, Erembodegem, Belgium). Briefly, 24 or 72 h after treatment, cells were lysed and incubated first in protease buffer and then for 2 h at 371C with Ac-DEVD-AMC substrate (1 mg ml À1 ). The enzyme-catalysed release of fluorescent AMC was measured, by referring to a standard curve, with a fluorimeter, at 380 nm excitation and 440 nm emission wavelengths.Measurement of phosphatidylserine translocation using AnnexinV -FITC Phosphatidylserine outer translocation on treated cells was detected by flow cytometry (BD FACScan and CellQuest software) using AnnexinV -FITC binding (1 mg ml À1 ) (BD Biosciences) and PI (2 mg ml À1 ) counterstaining.TUNEL a...

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Section: Resultsmentioning

confidence: 99%

Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour

et al. 2003

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“…More recently, it was demonstrated that it shows antimicrobial properties against pathogens like Staphylococcus epidermidis , Shigella dysenteriae , Pseudomonas fluorescens and Candida albicans , among others [3]. The drug is classified as non-genotoxic [4,5] and non-mutagenic [6], moderately toxic based on LD 50 values obtained from three different experimental models and using two different routes of administration (oral and intraperitoneal) and a slight irritant of the skin and eyes [1,2].…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Sublimation and Vapor Pressure of 2-(2-Nitrovinyl) Furan (G-0) Using Thermogravimetric Analysis: Effects of Complexation with Cyclodextrins

et al. 2015

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Abstract:In the present work, the sublimation of crystalline solid 2-(2-nitrovinyl) furan (G-0) in the temperature range of 35 to 60 °C (below the melting point of the drug) was studied using thermogravimetric analysis (TGA). The sublimated product was characterized using Fourier-transformed-infrared spectroscopy (FT-IR) and thin layer chromatography (TLC). The sublimation rate at each temperature was obtained using the slope of the linear regression model and followed apparent zero-order kinetics. The sublimation enthalpy from 35 to 60 °C was obtained from the Eyring equation. The Gückel method was used to estimate the sublimation rate and vapor pressure at 25 °C. Physical mixtures, kneaded and freeze-dried complexes were prepared with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and sulfobutyl ether-β-cyclodextrin OPEN ACCESSMolecules 2015, 20 15176(SBE-β-CD) and analyzed using isothermal TGA at 50 °C. The complexation contributed to reducing the sublimation process. The best results were achieved using freeze-dried complexes with both cyclodextrins.

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“…It has been suggested that micronuclei formation may be an important process in carcinogenesis (Van Goethem et al 1993). So, micronuclei assay will be of great significance in the detection of cancer (Gonzalez Borroto et al 2001). According to several authors, the occurrence of micronuclei has been interpreted as an indicator of clastogenic and aneugenic effects (Walker et al 1996, Fenech et al 2003, Çavas and Ergene-Gözükara 2005.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Blebs Assay for Genome Instability in <i>Phaseolus vulgaris</i> L.

Kumar

Chaudhary

2015

CYTOLOGIA

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Summary Micronuclei are extra nuclear structures, formed by the exclusion of chromosomes during cell division. The genotoxicity of a compound and its impact on the genome can be assessed via micronuclei formation. The present study has been undertaken to evaluate the mutagenic effect of the alkylating agent EMS on the meiotic behavior of pollen mother cells of Phaseolus vulgaris L. The cytological analysis revealed the induction of micronuclei at all the three administered concentrations of EMS, viz. 0.1, 0.3 and 0.5%. Besides micronuclei formation, other meiotic abnormalities associated with chromosomal segregation, such as stickiness, laggard, bridge, multivalent, etc., were also reported at metaphase I/II and anaphase I/II. The micronuclei formed would have two fates either it remains until the tetrad stage or is expelled out in the form of microcytes which will give rise to sterile pollen grains affecting the pollen fertility. The present study also documents the first instance of nuclear budding in Phaseolus vulgaris L. It is contemplated that these nuclear buds will later on convert into micronuclei. The micronuclei formation results in partial elimination of the genome, which could be efficiently utilized in breeding programmes for the production of addition and substitution lines. Similarly, haploid lines could also be produced by the complete loss of genome. It is therefore essential to understand the biological aspects of micronuclei formation, its consequences on the cell carrying it and other factors related to it so that in the future, it could be used as a marker of genetic damage and also be utilized in breeding programmes.

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Genotoxic evaluation of the furylethylene derivative 2-furyl-1-nitroethene in cultured human lymphocytes

Cited by 19 publications

References 22 publications

Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour

Micronuclei to detect in vivo chemotherapy damage in a p53 mutated solid tumour

Characterization of the Sublimation and Vapor Pressure of 2-(2-Nitrovinyl) Furan (G-0) Using Thermogravimetric Analysis: Effects of Complexation with Cyclodextrins

Nuclear Blebs Assay for Genome Instability in <i>Phaseolus vulgaris</i> L.

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