Mitotic recombination: a genotoxic effect of the antidepressant citalopram in <i>Aspergillus nidulans</i>

Franco, Claudinéia C. S.; Castro-Prado, Juliana de; Rosada, Lúcia J; Sant’Anna, Juliane Rocha de; Castro-Prado, Marialba Avezum Alves de

doi:10.1258/ebm.2010.010159

Cited by 6 publications

(6 citation statements)

References 44 publications

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“…The results of this study are in good agreement with those reported by others, as indicated below. For instance, citalopram induced apoptosis in a human leukemic cell line [4], and it showed a strong recombinogenic effect in Aspergillus nidulans (at 50, 75 and 100 mmol/L) [38]. Furthermore, genotoxic effects of citalopram have been reported as chromosomal aberrations in Chinese hamster lung fibroblasts in vitro, as mutations in Ames assays [39], and as anti-neoplastic properties [40].…”

Section: Resultsmentioning

confidence: 99%

Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster

Gürbüzel

Oral

Kızılet

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Section: Resultsmentioning

confidence: 99%

Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster

Gürbüzel

Oral

Kızılet

et al. 2012

Mutation Research/Genetic Toxicology and Environmental Mutagene

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“…Conclusively, the finding of the present study indicates that citalopram is a genotoxic agent and produces genetic damages that end up as olive tail moment or MN. These generally positive genotoxic responses with citalopram are in agreement with positive responses for chromosomal aberrations in Chinese hamster lung fibroblasts, bacterial reverse mutation in S. typhimurium TA98 and TA1537 (Snyder et al ., ; Snyder et al ., ), the strong recombinogenic effect of citalopram in A. nidulans diploid cells (Franco et al ., ) and the determination that it is carcinogenic in the small intestine in rats (Snyder et al ., ; Snyder et al ., ). On the other hand, an increase in the mutant frequency was not induced by citalopram at the Hprt locus in mouse lymphoma cells or in a coupled in vitro / in vivo unscheduled DNA synthesis assay in the rat liver.…”

Section: Resultsmentioning

confidence: 99%

Comet‐FISH studies for evaluation of genetic damage of citalopram in somatic cells of the mouse

Attia

Ashour

Bakheet

2013

J of Applied Toxicology

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Damage to DNA can lead to many different acute and chronic pathophysiological conditions, ranging from cancer to endothelial damage. The present study was designed to evaluate the DNA damage of an antidepressant drug, citalopram, at the recommended human doses in somatic cells of mice in vivo. Mice exposed to citalopram at varying oral doses of 12 or 24 mg kg(-1) for 7 days exhibited a significant increase in the level of DNA-strand breaking and micronuclei formation as detected by a bone marrow comet assay and micronucleus test, respectively. Furthermore, using fluorescence in situ hybridization (FISH) analysis with the centromeric mouse-satellite DNA-probe for erythrocyte micronuclei it could be shown that citalopram is aneugen as well as clastogen in somatic cells in vivo. Colchicine (COL) and mitomycin C (MMC) were used as positive controls and these compounds produced the expected responses. Both the clastogenic and the aneugenic potential of citalopram can give rise to the development of secondary tumours and abnormal reproductive outcomes. Overall, the results suggest that citalopram at the recommended human doses induces some genetic alterations, which can adversely affect the normal cellular functioning in mice. The mechanism(s) by which citalopram cause this adverse effect appear related, in part, to primary DNA strand breakage as detected by the comet assay as well as clastogenic and aneugenic events as detected by the FISH assay. Therefore, the clinical use of citalopram must be weighed against the risks of genetic damages in citalopram users.

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“…Based on computer modeling and energy calculations of drug/DNA complexes, the source of genotoxicity caused by citalopram was proposed to be an N-dialkyl group responsible for DNA intercalation (Synder et al , 2006). Citalopram was also shown to induce genotoxicity via DNA strand breaks and mitotic recombination in Aspergillus nidulans and Drosophila melanogaster (Franco et al , 2010; Gürbüzel et al , 2012).…”

Section: Introductionmentioning

confidence: 99%

In vitro cytogenotoxic evaluation of sertraline

İstifli

Çelik

Hüsunet

et al. 2018

Interdisciplinary Toxicology

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Sertraline (SRT) is an antidepressant agent used as a neuronal selective serotonin-reuptake inhibitor (SSRI). SRT blocks serotonin reuptake and increases serotonin stimulation of somatodendritic serotonin 1A receptor (5-HT1AR) and terminal autoreceptors in the brain. In the present study, the genotoxic potential of SRT was evaluated using cytokinesis-block micronucleus (CBMN) cytome assay in peripheral blood lymphocytes of healthy human subjects. DNA cleavage-protective effects of SRT were analyzed on plasmid pBR322. In addition, biochemical parameters of total oxidant status (TOS) and total antioxidant status (TAS) in blood plasma were measured to quantitate oxidative stress. Human peripheral blood lymphocytes were exposed to four different concentrations (1.25, 2.5, 3.75 and 5 μg/mL) of SRT for 24- or 48-h treatment periods. In this study, SRT was not found to induce MN formation either in 24- or 48-h treatment periods. In contrast, SRT concentration-dependently decreased the percentage of MN and MNBN (r=–0.979, p<0.01; r=–0.930, p<0.05, respectively) when it was present for the last 48 hr (48-h treatment) of the culture period. SRT neither demonstrated a cleavage activity on plasmid DNA nor conferred DNA protection against H2O2. The application of various concentrations of SRT significantly increased the TOS and oxidative stress index (OSI) in human peripheral blood lymphocytes for both the 24- and 48-h treatment periods. Morover, the increase in TOS was potent as the positive control MMC at both treatment times. However, SRT did not alter the TAS levels in either 24- or 48-h treatment periods when compared to control. In addition, exposing cells to SRT caused significant decreases in the nuclear division index at 1.25, 2.50 and 3.75 μg/mL in the 24-h and at the highest concentration (5 μg/mL) in the 48-h treatment periods. Our results suggest that SRT may have cytotoxic effect via oxidative stress on cultured human peripheral blood lymphocytes.

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Mitotic recombination: a genotoxic effect of the antidepressant citalopram in Aspergillus nidulans

Cited by 6 publications

References 44 publications

Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster

Genotoxic evaluation of selective serotonin-reuptake inhibitors by use of the somatic mutation and recombination test in Drosophila melanogaster

Comet‐FISH studies for evaluation of genetic damage of citalopram in somatic cells of the mouse

In vitro cytogenotoxic evaluation of sertraline

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