Genotoxicity Dotaz Zobrazit nápovědu
- Klíčová slova
- Genotoxicity testing, In silico prediction, In vivo relevance of in vitro geotoxicity tests, Mammalian in vitro genotoxicity tests,
- MeSH
- biomedicínský výzkum výchova metody MeSH
- karcinogeneze chemicky indukované MeSH
- mezioborová komunikace MeSH
- nebezpečné látky toxicita MeSH
- testy genotoxicity metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- úvodníky MeSH
- Názvy látek
- nebezpečné látky MeSH
Health care facilities use for therapeutic purposes, diagnostics, research, and disinfection a high number of chemical compounds, such as pharmaceuticals (e.g. antibiotics, cytostatics, antidepressants), disinfectants, surfactants, metals, radioactive elements, bleach preparations, etc. Hospitals consume significant amounts of water (in the range of 400 to 1200 liters/day/bed) corresponding to the amount of wastewater discharge. Some of these chemicals are not eliminated in wastewater treatment plants and are the source of pollution for surface and groundwater supplies. Hospital wastewater represents chemical and biological risks for public and environmental health as many of these compounds might be genotoxic and are suspected to contribute to the increased incidence of cancer observed during the last decades. The changes of the genetic information can have a lethal effect, but more often cause tumor processes or mutations in embryonic development causing serious defects. A review of the available literature on the mutagenicity/genotoxicity of medical facilities wastewater is presented in this article.
- MeSH
- chemické látky znečišťující vodu toxicita MeSH
- lidé MeSH
- odpadní voda toxicita MeSH
- testy genotoxicity metody MeSH
- zdravotnická zařízení * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- chemické látky znečišťující vodu MeSH
- odpadní voda MeSH
The fate and effects of cytostatic (anticancer or antineoplastic) pharmaceuticals in the environment are largely unknown, but they can contaminate wastewater treatment effluents and consequently aquatic ecosystems. In this paper, we have focused on five cytostatic compounds used in high amounts (cyclophosphamide, cisplatin, 5-fluorouracil, doxorubicin, and etoposide), and we have investigated their ecotoxicity in bacterial Pseudomonas putida growth-inhibition test, algal Pseudokirchneriella subcapitata growth-inhibition test, and Dapnia magna acute immobilization test. Genotoxicity also was assessed with Escherichia coli SOS-chromotest (with and without metabolic activation) and the GreenScreen Assay using yeast S. cerevisiae. All tested compounds showed significant effects in most of the assays with lowest-observed-effect concentrations and concentrations causing 50% effects (EC50s) values ranging within microg/L to mg/L. The most toxic compound was 5-fluorouracil in the assays with P. putida (EC50 = 0.027 mg/L) and P. subcapitata (EC50 = 0.11 mg/L), although cisplatin and doxorubicin were the most toxic to D. magna (EC50 = 0.64 and 2.0 mg/L, respectively). These two chemicals were also the most genotoxic in the SOS-chromotest (minimum genotoxic concentrations [MGC] = 0.07-0.2 mg/L), and 5-fluorouracil was the most genotoxic in the eukaryotic yeast assay (MGC = 0.02 mg/L). Our investigation seems to indicate generally lower risks of acute effects at concentrations expected in the environment. However, some effective concentrations were relatively low and chronic toxicity of cytostatics (and/or their transformation products), as well as specific sources of human pharmaceuticals such as hospital effluents, require research attention.
- MeSH
- látky znečišťující životní prostředí toxicita MeSH
- protinádorové látky toxicita MeSH
- testy genotoxicity MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- látky znečišťující životní prostředí MeSH
- protinádorové látky MeSH
Chromosome analysis was conducted for peripheral lymphocytes of 23 printers exposed to toluene concentrations of 590 mg/m3 in a rotary machine workshop and to rotogravure printing inks. The percentages of aberrant cells were 2.30 in the printers and 1.46 in the control group (n = 22) (p < .05). The concentration of hippuric acid in printers was significantly higher than in the control group (p < .01), and the level of blood toluene at the end of the workshift was 0.500 mg/l. The authors also examined rotogravure printing inks-considered a potential source of genotoxic polycyclic aromatic hydrocarbons because they contained carbon black-their use in printing plants, and previous documentation of increased chromosomal aberrations in rotogravure printers. Only milligrams of fluorene and phenanthrene per gram of the printing inks were found; no polycyclic aromatic hydrocarbons with carcinogenic properties were discovered in the inks. The authors used Salmonella typhimurium indicator strains TA 98, TA 100, TA 1537, and YG 1041 in spot tests and indicator strains TA 98 and TA 100 in plate-incorporation assays to determine that there was no bacterial mutagenicity of all four colors of rotogravure inks. Urinary mutagenicity, which was evaluated with a microsuspension assay containing YG 1041 indicator strain both in the presence and absence of metabolic activation, was also studied. No significant difference in bacterial mutagenicity was found between the exposed and control groups. The increased percentage of aberrant cells in printers can be explained by exposure to genotoxicants that are not excreted in urine. Toluene was the most likely cause of the aberration.
- MeSH
- chromozomální aberace MeSH
- dospělí MeSH
- inkoust MeSH
- lidé středního věku MeSH
- lidé MeSH
- pracovní expozice analýza MeSH
- testy genotoxicity metody MeSH
- tiskařství MeSH
- toluen škodlivé účinky moč MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- toluen MeSH
The genotoxic and embryotoxic effects of phosphonomethoxyalkylpurines, a new group of antiviral agents, decrease in the following order: PMEG > PMEthioG > PMEDAP > PMEA > (R)-PMPDAP = (R)-PMPA. Results of the present study are fully consistent with the previously found efficacy of their diphosphates to inhibit the replicative DNA polymerases. The marked genotoxicity of PMEG and PMEthioG is comparable to that of mitomycin C, whereas the moderate genotoxicity of PMEA is comparable to that of AZT. (R)-PMPDAP and (R)-PMPA did not induce any structural aberrations of chromosomes under the experimental conditions.
- MeSH
- adenin analogy a deriváty chemie toxicita MeSH
- antivirové látky chemie toxicita MeSH
- buněčné linie MeSH
- guanin analogy a deriváty chemie toxicita MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- molekulární struktura MeSH
- mutageny chemie toxicita MeSH
- organofosfonáty * MeSH
- organofosforové sloučeniny chemie toxicita MeSH
- potkani inbrední BN MeSH
- potkani inbrední LEW MeSH
- puriny chemie toxicita MeSH
- tenofovir MeSH
- teratogeny chemie toxicita MeSH
- testy genotoxicity MeSH
- thioguanin chemie toxicita MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 9-((2-phosphonylmethoxy)ethyl)guanine MeSH Prohlížeč
- 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine MeSH Prohlížeč
- 9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine MeSH Prohlížeč
- adefovir MeSH Prohlížeč
- adenin MeSH
- antivirové látky MeSH
- guanin MeSH
- mutageny MeSH
- organofosfonáty * MeSH
- organofosforové sloučeniny MeSH
- puriny MeSH
- tenofovir MeSH
- teratogeny MeSH
- thioguanin MeSH
BACKGROUND: Sanguinarine (SG) has been reported to form DNA adducts in vitro and increase the levels of DNA single strand breaks in the blood and bone marrow of mice treated intraperitoneally with SG. Recently, we showed no genotoxic effects of orally administrated 120 mg/kg feed Macleaya cordata extract (a mixture of sanguinarine and chelerythrine) in pigs or rats in 90-day studies. The goal of this paper was to assess the possible genotoxicity of M. cordata extract when included as a dietary admixture to rodents at concentrations providing 600 mg/kg feed and 100, 7000 or 14000 mg/kg feed Sangrovit (natural feed additive containing M. cordata extract and powdered M. cordata) in a 90-day pilot study. METHODS AND RESULTS: The rats consumed ad libitum either the standard diet or the diets containing 367 ppm of sanguinarine and chelerythrine in M. cordata extract, and 5, 330, or 660 ppm of total alkaloids in Sangrovit for 90 days. The DNA adducts formation in liver was analyzed by (32)P-postlabeling technique and DNA single strand breaks in lymphocytes were evaluated by Comet assay. The results showed that M. cordata extract and/or Sangrovit induced no DNA damage to rat lymphocytes or hepatocytes after 90-days oral administration. CONCLUSIONS: Data from the studies described in this paper and the fact that Sangrovit given to the rats in our experiments were higher than the recommended dose (50 to 100 mg/kg feed), argue strongly in favour of the use of Sangrovit in live stock.
- MeSH
- adukty DNA účinky léků MeSH
- benzofenantridiny toxicita MeSH
- isochinoliny toxicita MeSH
- jednovláknová DNA účinky léků MeSH
- krmivo pro zvířata * MeSH
- krysa rodu Rattus MeSH
- Papaveraceae toxicita MeSH
- poškození DNA účinky léků MeSH
- potkani Wistar MeSH
- potravní doplňky toxicita MeSH
- rostlinné extrakty toxicita MeSH
- testy genotoxicity MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adukty DNA MeSH
- benzofenantridiny MeSH
- chelerythrine MeSH Prohlížeč
- isochinoliny MeSH
- jednovláknová DNA MeSH
- rostlinné extrakty MeSH
- sanguinarine MeSH Prohlížeč
- MeSH
- abnormality vyvolané léky etiologie MeSH
- biotransformace MeSH
- embryo savčí účinky léků MeSH
- karcinogeny toxicita MeSH
- lidé MeSH
- metronidazol škodlivé účinky metabolismus farmakokinetika toxicita MeSH
- mutageny toxicita MeSH
- poškození DNA MeSH
- těhotenství MeSH
- testy genotoxicity MeSH
- testy karcinogenity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- karcinogeny MeSH
- metronidazol MeSH
- mutageny MeSH
Toxaphene (CAS No. 800-35-2) is a complex mixture of several hundred components that was used worldwide primarily as an agricultural pesticide with insecticide effects in the second half of the 20th century. In vitro investigations of the genotoxicity and mutagenicity of toxaphene were generally described in the literature, but they provided somewhat equivocal results. We re-evaluated the genotoxicity of technical toxaphene in two prokaryotic systems. The SOS Chromotest showed high sensitivity to toxaphene: three concentrations (40, 20 and 10 mg/l) were clearly positive and the dose-response effect was evident. In the umuC assay, a dose-dependent increase in genotoxic activity was observed at toxaphene concentrations from 2.5 to 40.0 mg/l, but these results were found to be not significant. The genotoxicity of toxaphene and its photodegradation products after UV-irradiation (3-6-9 h) at concentrations ranging from 7.5 to 60.0 mg/l was also examined in this study. An irradiated solution of technical toxaphene after 3 h showed no significant evidence of bacterial growth inhibition. However, exposure of Salmonella to 6 h UV-irradiated toxaphene showed a toxic effect compared with the negative control. After 9 h irradiation, a decrease of bacterial growth was observed. Activity of beta-galactosidase in the presence of a toxaphene solution was significantly increased after 6 and 9 h irradiation, reaching values that were 2.4- and 3.1-fold higher, respectively, than the control, which exceeded the criteria of significant genotoxicity. These results show that while technical toxaphene is a weak, direct-acting mutagen in some bacterial tests, a dose-dependent toxicity and genotoxicity of its photoproducts could be conclusively demonstrated by the umuC test.
- MeSH
- DNA-dependentní DNA-polymerasy MeSH
- insekticidy chemie metabolismus toxicita MeSH
- proteiny z Escherichia coli genetika metabolismus MeSH
- Salmonella typhimurium účinky léků genetika metabolismus MeSH
- SOS odpověď (genetika) * MeSH
- světlo * MeSH
- testy genotoxicity * metody MeSH
- toxafen chemie metabolismus toxicita MeSH
- ultrafialové záření MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA-dependentní DNA-polymerasy MeSH
- insekticidy MeSH
- proteiny z Escherichia coli MeSH
- toxafen MeSH
- UmuC protein, E coli MeSH Prohlížeč
Growing worldwide efforts to replace (reduce) animal testing and to improve alternative in vitro tests which may be more efficient in terms of both time, cost and scientific validity include also genotoxicity/mutagenicity endpoints. The aim of the review article was to summarize currently available in vitro testing approaches in this field, their regulatory acceptance and recommended combinations for classification of chemicals. A study using the combination of Comet Assay performed on two cell lines and the Chromosomal Aberration test on human peripheral lymphocytes was performed with the aim to predict the genotoxic potential of selected paraben esters, serving as a model chemical group. Parabens are widely used in consumer products as preservatives and have been reported to exhibit inconclusive results in numerous genotoxicity studies. The Comet Assay identified Ethylparaben and Benzylparaben as potentially genotoxic. The Chromosomal Aberration test revealed weak genotoxic potential in case of Ethylparaben and positive genotoxicity in case of Butylparaben, Propylparaben and Isopropylparaben. The main reasons for variability seem to be limited water solubility of parabens, determining their bioavailability at the cellular level, and absence of metabolic activation in the Comet Assay. The results confirmed that the Comet Assay should serve as a screening test and should not be used as a stand-alone method for classification of genotoxicity. The weight of evidence approach in risk assessment should be supported with data generated with the use of human relevant in vitro methods based on cells / tissues of human origin.
- MeSH
- alternativy testů na zvířatech * MeSH
- buněčné linie keratinocytů HaCaT MeSH
- chromozomální aberace chemicky indukované MeSH
- hodnocení rizik MeSH
- kometový test MeSH
- lidé MeSH
- lymfocyty účinky léků patologie MeSH
- mikrojaderné testy MeSH
- mikrojádra chromozomálně defektní chemicky indukované MeSH
- mutageneze účinky léků MeSH
- parabeny toxicita MeSH
- poškození DNA * MeSH
- testy genotoxicity * MeSH
- viabilita buněk účinky léků MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- srovnávací studie MeSH
- Názvy látek
- parabeny MeSH
The bacterial VITOTOX genotoxicity test was used to screen water samples collected from three different stations along the banks of the river Musi, in Hyderabad, India. Water was collected at three stations that differed from each other in the nature of the surrounding industrial and other activities. A number of different pollutants were also measured in water, soil and air samples. The three stations were found highly polluted and different with regard to the genotoxicity and toxicity of their samples. These results demonstrate the need for further biological studies in this area to generate valuable data on genomic instability, risk assessment of cancer, and to provide avenues for risk management.
- MeSH
- arochlory farmakologie toxicita MeSH
- biologické toxiny analýza MeSH
- časové faktory MeSH
- Escherichia coli genetika MeSH
- játra cytologie enzymologie MeSH
- krysa rodu Rattus MeSH
- látky znečišťující půdu analýza toxicita MeSH
- látky znečišťující vodu analýza toxicita MeSH
- mikrozomy enzymologie MeSH
- řeky chemie MeSH
- Salmonella typhimurium genetika MeSH
- testy genotoxicity * metody MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Indie MeSH
- Názvy látek
- arochlory MeSH
- biologické toxiny MeSH
- látky znečišťující půdu MeSH
- látky znečišťující vodu MeSH