1,721,002 research outputs found
Genotoxic effects in nurses occupationally exposed to antineoplastic drugs: meta-analysis of data
No full textAntineoplastic drugs (AD) are a group of chemicals known to be mutagenic/carcinogenic. Concern has raised about possible genotoxic hazards for healthcare personnel handling these drugs, as occupational exposure to AD is still frequent in hospital settings despite significant safety policy improvements. Biomonitoring of genotoxic hazards has been reported in several studies, mainly by the use of cytogenetic assays, such as analysis of chromosome aberrations (CA) or micronuclei (MN) in peripheral blood lymphocytes. We have performed a systematic review of molecular epidemiology studies of occupational exposure to AD in the attempt to discover whether a general trend could be evinced on this topic.
A structured computer search on PubMed was performed for molecular epidemiological studies reporting results of primary researches with cross-sectional evaluation of MN in personnel occupationally exposed to AD. Selected studies had to report average (± SD or SEM) group data for frequency of structural/numerical chromosome aberrations and/or micronuclei.
The systematic review identified 28 studies. As a measure of effect we calculated the ratio of means (RoM), defined as the mean value in the exposed group divided by the mean value in the control group, useful to compare studies with outcomes expressed in different units (e.g., %, etc.). To perform the meta-analysis we used the software Review Manager (RevMan 5.1) by The Cochrane Collaboration. The majority of the studies had shown a high level of MN in healthcare personnel exposed to AD, compared to unexposed subjects, RoM = 5,02 [4,99-5,04]. The asymmetry in the lower part of the Funnel plot is due to small sample size of the studies in literature.
In according to the prognostic value of MN, the studied population appears to be much more at risk to develop cancer than unexposed nurses. This finding clearly indicates the necessity to improve some steps in the administration process of AD to appropriately cope with genotoxic risk.
Key messages
Healthcare personnel handling AD is exposed to a high genotoxic risk
Guidelines for handling AD, as well as safety recommendation, should be issue
Investigation of in vitro cytotoxicity and genotoxicity of a new organoselenium compound: PhSeZnCl
No full textThe aim of the present study was to evaluate the ability of PhSeZnCl to induce cytotoxicity and/or genetic damage in vitro. Human hepatoma cells, HepG2, were exposed to increasing concentrations of PhSeZnCl (from 10 to 0,1 μM) for 4 h at 37oC. Cytotoxicity was assessed either by acridine orange/DAPI staining and trypan blue exclusion test. Non cytotoxic doses were further analysed for genotoxicity by means of the single cell microgel (comet) assay. The results showed that exposure of HepG2 cells to the given compound resulted in a significant cytotoxic effect up to a concentrations of 2 μM. With respect to genotoxicity, only the highest non cytotoxic concentrations of PhSeZnCl (1 μM) produced significant genetic damage, with a high proportion of apoptotic cell. Since apoptosis induced by DNA damage is an important mechanism of tumor suppression, further studies are required to clarify the genotoxic and apoptotis-inducing effects of PhSeZnCl
Preliminary in vitro safety assessment of a novel organoselenium compound: PhSeZnCl
No full textIntroduction: A number of novel synthetic organoselenium compounds are currently under development as promising anticancer, antioxidant and antimicrobial agents. However, the toxicity associated with selenium could be a limiting factor for their use in pharmacotherapy. The aim of the present study was to investigate the toxicity of PhSeZnCl, a new synthetic seleniorganic compound with GPx-like activity.
Methods: Human hepatoma (HepG2) cells were exposed in vitro to different concentrations of PhSeZnCl. Trypan blue dye exclusion test and acridine orange/DAPI double staining were used to determine cytotoxicity. The three highest non-cytotoxic doses of PhSeZnCl were further analyzed for the effects on DNA damage, apoptosis, cell cycle progression and inflammation. The single-cell-microgel electrophoresis (“comet”) assay and the micronucleus (MN) test were conducted for genotoxicity assessment. Late apoptotic cells and cell cycle progression were evaluated by DNA content analysis using the quantitative DNA-binding dye DAPI. Decrease in mitochondrial membrane potential, which occurs in early apoptotic cells, was detected using the lipophilic cationic dye JC-1. Lastly, levels of pro-inflammatory cytokine IL-8 were quantified using commercially available ELISA kits.
Results: Cell viability assays showed that PhSeZnCl produced cytotoxic effects in HepG2 cells up to a concentration of 0.4 mM. Comet assay revealed a significant increase of the extent of DNA damage at the highest non-cytotoxic dose tested (0.2 mM). Conversely, the frequencies of MN in treatment cells were found to be comparable to those of the control. Apoptosis assays and DNA content analysis revealed a time-dependent increase in the proportion of both early and late apoptotic cells and a cell cycle arrest in the G2/M phase following exposure to PhSeZnCl 0.2 mM. For this dose, IL-8 protein levels were also found to be significantly increased with respect to untreated cells.
Conclusion: Our results indicate that only the highest non-cytotoxic dose of PhSeZnCl (0.2 mM) cause inflammatory and DNA damaging effects on HepG2 cells. The absence of fixed cytogenetic damage (i.e. micronuclei) could be explained by the induction of cell cycle arrest and apoptotic pathways, which determine the removal of cells with irreparable DNA damage
Genotoxic effects in nurses occupationally exposed to antineoplastic drugs: meta-analysis of data.
No full textAntineoplastic drugs (AD) are a group of chemicals known to be mutagenic/carcinogenic. Concern has raised about possible genotoxic hazards for healthcare personnel handling these drugs, as occupational exposure to AD is still frequent in hospital settings despite significant safety policy improvements. Biomonitoring of genotoxic hazards has been reported in several studies, mainly by the use of cytogenetic assays, such as analysis of chromosome aberrations (CA) or micronuclei (MN) in peripheral blood lymphocytes. We have performed a systematic review of molecular epidemiology studies of occupational exposure to AD in the attempt to discover whether a general trend could be evinced on this topic.
A structured computer search on PubMed was performed for molecular epidemiological studies reporting results of primary researches with cross-sectional evaluation of MN in personnel occupationally exposed to AD. Selected studies had to report average (± SD or SEM) group data for frequency of structural/numerical chromosome aberrations and/or micronuclei.
The systematic review identified 28 studies. As a measure of effect we calculated the ratio of means (RoM), defined as the mean value in the exposed group divided by the mean value in the control group, useful to compare studies with outcomes expressed in different units (e.g., %, etc.). To perform the meta-analysis we used the software Review Manager (RevMan 5.1) by The Cochrane Collaboration. The majority of the studies had shown a high level of MN in healthcare personnel exposed to AD, compared to unexposed subjects, RoM = 5,02 [4,99-5,04]. The asymmetry in the lower part of the Funnel plot is due to small sample size of the studies in literature.
In according to the prognostic value of MN, the studied population appears to be much more at risk to develop cancer than unexposed nurses. This finding clearly indicates the necessity to improve some steps in the administration process of AD to appropriately cope with genotoxic risk.
Key messages
Healthcare personnel handling AD is exposed to a high genotoxic risk
Guidelines for handling AD, as well as safety recommendation, should be issue
In vitro risk assessment of pure trans-anethole and of a herbal extract from Foeniculum vulgare (fennel), containing trans-anethole.
No full text
Nanoparticelle negli ambienti di lavoro: messa a punto di metodi per il campionamento e per la valutazione della genotossicità
No full textLe nanoparticelle (NP) sono, per definizione, caratterizzate dal possedere almeno una dimensione inferiore a 100 nm. Tale limite è in realtà arbitrario in quanto alcune proprietà caratteristiche delle NP (es. la possibilità di essere internalizzate nel citoplasma) si rilevano anche in materiali con dimensioni sub-microniche non superiori a 300 nm. Le NP sono prodotte principalmente in processi nanotecnologici e sono utilizzate per svariati scopi, (es. formulazione di cosmetici, vernici, tessuti, articoli sportivi, hard disks per registrazione dati ad altissima densità, superfici autopulenti,
sistemi per diagnostica medica), ma possono anche essere presenti nell’ambiente di vita e di lavoro (es. prodotti secondari dei processi di combustione). La potenziale esposizione di un numero sempre più ampio di soggetti, dovuta alla crescente diffusione di NP, e i pochi dati disponibili sui rischi per la salute, evidenziano la necessità di implementare le conoscenze riguardanti i possibili effetti biologici indotti dalla esposizione a NP. A tale scopo il Dip. di Specialità Medico-Chirurgiche e Sanità Pubblica dell’Università di Perugia e la CONTARP Umbria hanno avviato
una collaborazione avente come obiettivo la definizione di una metodica, la più semplice e fruibile possibile, per caratterizzare gli effetti genotossici delle particelle sub-microniche presenti in alcuni ambienti di lavoro (nello specifico in aziende che svolgono lavori in sottosuolo e in aziende metalmeccaniche). L’applicabilità di tale metodica potrebbe consentire la segnalazione precoce della potenzialità morbigena delle NP e permettere al medico competente di predisporre adeguati protocolli sanitari. Nella prima fase dello studio sono stati messi a punto due test di genotossicità
in vitro (test della cometa e test del micronucleo) su cellule polmonari umane utilizzando come NP modello TiO2 e ZnO. Successivamente si è proceduto alla ottimizzazione delle metodiche di campionamento delle particelle sub-microniche presenti negli ambienti lavorativi. Infine, i test della cometa e del micronucleo sono stati utilizzati per la valutazione della genotossicità delle particelle campionate.
I risultati ottenuti indicano che: (1) i due test presentano una buona sensibilità nella rilevazione dell’attività genotossica delle NP; (2) il sistema di campionamento di particelle sub-microniche utilizzato risulta idoneo allo studio in quanto in grado di raccogliere particolato di 5 diverse classi granulometriche l’ultima delle quali costituita da particelle sub-microniche (minore di 250 nm); (3) per quanto riguarda le NP campionate negli ambienti di lavoro, solo le particelle sub-microniche sono risultate genotossiche
Primary DNA damage in welders occupationally exposed to extremely-low-frequency magnetic fields (ELF-MF)
No full textBACKGROUND: Electric arc welding is known to involve considerable exposure to extremely-low-frequency magnetic fields (ELF-MF; 50 Hz). The aim of the present study was to evaluate individual exposure to ELF-MF during arc welding and to assess the eventually associated genotoxic hazard by evaluating primary DNA damage.
METHODS: The study group comprised 21 electric arc welders (exposed) and 21 non-exposed control subjects (healthy blood donors). Occupational exposure to ELF-MF was measured using personal dosimeters worn during one complete work-shift (7 am to 5 pm). The extent of primary DNA damage was measured in peripheral blood leukocytes with the standard procedure of the alkaline comet assay.
RESULTS: Tail length showed to have similar values in welders and controls. Whereas, the data showed a significant decrease for tail intensity (p = 0.01) and tail moment (p = 0.02) counts in exposed subjects compared to controls.
CONCLUSIONS: The different results of our present study and published investigations from other research groups reporting positive results in the comet assay might be a result of different chromium and/or nickel (or other metals) exposure levels, which lead to DNA-protein cross-links at lower concentrations and DNA single-strand breakages at higher concentrations. Since these results are derived from a small-scale pilot study, a larger scale study should be undertaken
Occupational exposure to cytostatic/antineoplastic drugs and cytogenetic damage measured using the lymphocyte cytokinesis-block micronucleus assay: A systematic review of the literature and meta-analysis
No full textMany studies have reported the occurrence of work-environment contamination by antineoplastic drugs (ANPD), with significant incorporation of trace amounts of these hazardous drugs in hospital personnel. Given the ability of most ANPD to actively bind DNA, thus inducing genotoxic effects, it is of pivotal importance to assess the degree of genotoxic damage (i.e., residual genotoxic risk) in occupationally exposed subjects. The lymphocyte cytokinesis-block micronucleus (L-CBMN) assay is largely used for biological effect monitoring in subjects occupationally exposed to ANPD. In this study, we identified and analyzed the studies published reporting the use of the L-CBMN assay as biomarker of genotoxic risk in health care workers exposed to ANPD with the aim of performing meta-analysis and providing a meta-estimate of the genotoxic effect of exposure. We retrieved 24 studies, published from 1988 to 2015, measuring MN in peripheral blood lymphocytes in health care workers occupationally exposed to ANPD. In 15 out of the 24 studies (62.5%), increased MN frequencies were recognized in exposed subjects as compared to controls. The meta-analysis of MN frequency of the combined studies confirmed an association between occupational exposure to ANPD and cytogenetic effects with an overall meta-estimate of 1.67 [95% CI: 1.41-1.98]. In 16 out of the 24 studies (66.6%) at least one other genotoxicity biomarker, besides L-CBMN assay, was employed for biological effect monitoring. In several studies the effect of exposure to ANPD was evaluated also in terms of MN in exfoliated buccal cells. Other studies focused on genotoxicity endpoints, such as sister chromatid exchanges (3 studies), chromosome aberrations (6 studies), or primary DNA damage investigated by comet assay (7 studies). Overall, there was good agreement between other genotoxicity tests employed and L-CBMN assay outcomes
In vitro genotoxicity testing of botanical matrixes derived from Foeniculum vulgare (fennel)
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