Genetic toxicity of cytokines

Lazutka, Juozas R.

doi:10.1016/s0165-1161(96)00027-1

Cited by 21 publications

(17 citation statements)

References 67 publications

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“…Bothrops jararaca and B. atrox venoms promoted the release of TNF-a, IL-1b, IL-6, IL-10, and IFN-g (Petricevich et al, 2000;Zamunér et al, 2004). IFN-g and TNF-a were demonstrated to have a dose-dependent genotoxic effect in human peripheral blood lymphocyte cultures (Lazutka, 1996). Nevertheless, the component(s) of BMV responsible for its genotoxicity herein demonstrated remains to be determined.…”

Section: Discussionmentioning

confidence: 87%

In vitroandin vivogenotoxic evaluation ofBothrops moojenisnake venom

Zobiole

Caon

Bertól

et al. 2014

Pharmaceutical Biology

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Context: Bothrops moojeni Hoge (Viperidae) venom is a complex mixture of compounds with therapeutic potential that has been included in the research and development of new drugs. Along with the biological activity, the pharmaceutical applicability of this venom depends on its toxicological profile. Objective: This study evaluates the cytotoxicity and genotoxicity of the Bothrops moojeni venom (BMV). Material and methods: The in vitro cytotoxicity and genotoxicity of a pooled sample of BMV was assessed by the MTT and Comet assay, respectively. Genotoxicity was also evaluated in vivo through the micronucleus assay. Results: BMV displayed a 50% cytotoxic concentration (CC 50 ) on Vero cells of 4.09 mg/mL. Vero cells treated with 4 mg/mL for 90 min and 6 h presented significant (p50.05, ANOVA/NewmanKeuls test) higher DNA damage than the negative control in the Comet assay. The lower DNA damage found after 6 h compared with the 90 min treatment suggests a DNA repair effect. Mice intraperitoneally treated with BMV at 10, 30, or 80 mg/animal presented significant genotoxicity (p50.05, ANOVA/Newman-Keuls test) in relation to the negative control after 24 h of treatment. Contrary to the in vitro results, no DNA repair seemed to occur in vivo up to 96 h post-venom inoculation at a dose of 30 mg/animal. Discussion and conclusion: The results show that BMV presents cyto-and genotoxicity depending on the concentration/dose used. These findings emphasize the importance of toxicological studies, including assessment of genotoxicity, in the biological activity research of BMV and/or in the development of BMV-derived products.

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Section: Discussionmentioning

confidence: 87%

In vitroandin vivogenotoxic evaluation ofBothrops moojenisnake venom

Zobiole

Caon

Bertól

et al. 2014

Pharmaceutical Biology

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“…Given the cell cycle arrest produced by DNA damaging agents, and the occurrence of chromosomal (Lazutka, 1996), we studied metaphases in r-hu-IFNgtreated cell lines. Our results con®rm that r-hu-IFNg produces an enhancement of structural chromosome abnormalities including breaks, fragments and pulverization.…”

Section: Discussionmentioning

confidence: 99%

“…In view of the previously reported induction of genetic damages by IFNg in some mammalian cells (Lazutka 1996;Jaiswal et al, 2000), ®ve HM cell lines were examined in this respect (Table 1). The background level of chromosome abnormalities was low (510%) in QR, BT and FR but BL and MR exhibited a higher rate of spontaneous chromosome abnormalities.…”

Section: Cytogenetic Analyses Of Hm Cell Lines Exposed To R-hu-ifngmentioning

confidence: 99%

“…It has also been suggested that the antiproliferative activity of IFNs could be due to a STAT 1-mediated P21 WAF1/CIP1 transcription (Chin et al, 1996;Bromberg et al, 1996). The protein p21 WAF1 being a CDKI known to arrest cell cycle progression in response to dierent stimuli including DNA damaging agents (El-Deiry et al, 1994), such mechanism might be relevant with IFNs, since chromosome damage has been reported in IFN-treated cells (Lazutka, 1996). Along these lines, it is known that certain cell types treated with IFNg produce nitric oxide (NO), and it was recently shown that NO produced in response to IFN was capable to induce DNA damage (Boehm et al, 1997;Jaiswal et al, 2000); then the possibility of a cell cycle control in response to a DNA alteration deserves further investigation.…”

Section: Introductionmentioning

confidence: 99%

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Control of cell cycle progression in human mesothelioma cells treated with gamma interferon

et al. 2001

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Recombinant human interferon gamma (r-hu-IFNg) exerts both antitumoral activity in the early stages of human malignant mesothelioma and a cytostatic eect in human mesothelioma (HM) cell lines in vitro. The antiproliferative eect of interferons (IFNs) reported in a variety of cells has been attributed to several mechanisms. In order to progress in the understanding of HM cell growth modulation by r-hu-IFNg, modi®ca-tions of cell cycle progression and expression of key cell cycle regulator proteins in response to r-hu-IFNg were examined. Nine HM cell lines were studied, including one resistant to the antiproliferative eect of r-hu-IFNg. Except in the resistant cell line r-hu-IFNg produced an arrest in the G1 and G2-M phases of the cell cycle, associated with a reduction in both cyclin A and cyclin dependent kinase inhibitors (CDKIs) expression. Moreover cyclin B1/cdc2 activity was decreased. The present study provides the ®rst evidence of a G2-arrest in r-huIFNg-treated HM cell lines and indicates that HM cell lines, despite their tumorigenic origin still support cell cycle control. The cell cycle arrest induced by r-hu-IFNg seems to depend on cyclin regulation through p21 WAF1/ CIP1 -and p27 Kip1-independent mechanisms and is not directly related to the induced DNA damage. Oncogene (2001) 20, 1085 ± 1093.

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“…The induction of other cytokines is regulated by autocrine, juxtacrine or paracrine pathways in response to micro-environmental stimuli. Cytokines mediate the interaction between various cells, and cytokine dysregulation indicates disease pathogenesis (Lazutka, 1996). Pro-inflammatory cytokines are detected at low levels in body fluids and in tissues under normal circumstances.…”

Section: Human Skin Pro-inflammatory Cytokine Assessment: Skin Irritamentioning

confidence: 99%