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
Acetaldehyde is a highly reactive, DNA-damaging metabolite that is produced upon alcohol consumption1. Impaired detoxification of acetaldehyde is common in the Asian population, and is associated with alcohol-related cancers1,2. Cells are protected against acetaldehyde-induced damage by DNA crosslink repair, which when impaired causes Fanconi anaemia (FA), a disease resulting in failure to produce blood cells and a predisposition to cancer3,4. The combined inactivation of acetaldehyde detoxification and the FA pathway induces mutation, accelerates malignancies and causes the rapid attrition of blood stem cells5-7. However, the nature of the DNA damage induced by acetaldehyde and how this is repaired remains a key question. Here we generate acetaldehyde-induced DNA interstrand crosslinks and determine their repair mechanism in Xenopus egg extracts. We find that two replication-coupled pathways repair these lesions. The first is the FA pathway, which operates using excision-analogous to the mechanism used to repair the interstrand crosslinks caused by the chemotherapeutic agent cisplatin. However, the repair of acetaldehyde-induced crosslinks results in increased mutation frequency and an altered mutational spectrum compared with the repair of cisplatin-induced crosslinks. The second repair mechanism requires replication fork convergence, but does not involve DNA incisions-instead the acetaldehyde crosslink itself is broken. The Y-family DNA polymerase REV1 completes repair of the crosslink, culminating in a distinct mutational spectrum. These results define the repair pathways of DNA interstrand crosslinks caused by an endogenous and alcohol-derived metabolite, and identify an excision-independent mechanism.
- MeSH
- acetaldehyd chemie MeSH
- bodová mutace účinky léků genetika MeSH
- cisplatina chemie farmakologie MeSH
- DNA-dependentní DNA-polymerasy metabolismus MeSH
- DNA chemie MeSH
- ethanol chemie farmakologie MeSH
- Fanconiho anemie metabolismus MeSH
- mutageneze účinky léků MeSH
- nukleotidyltransferasy metabolismus MeSH
- oprava DNA * MeSH
- poškození DNA * účinky léků MeSH
- proteiny Xenopus metabolismus MeSH
- reagencia zkříženě vázaná chemie MeSH
- replikace DNA účinky léků fyziologie MeSH
- Xenopus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- acetaldehyd MeSH
- cisplatina MeSH
- DNA-dependentní DNA-polymerasy MeSH
- DNA MeSH
- ethanol MeSH
- nukleotidyltransferasy MeSH
- proteiny Xenopus MeSH
- reagencia zkříženě vázaná MeSH
- Rev1 protein, Xenopus MeSH Prohlížeč
BACKGROUND: Quercetin-3-O-β-D-glucopyranoside (isoquercitrin) and quercetin-3-O-rutinoside (rutin) are common components of a normal human diet and are increasingly used in food supplements. Here their effect on mutagenesis and immunity is shown. RESULTS: The in vitro (anti)mutagenic potential was compared with that of quercetin using the Ames test in Salmonella typhimurium His(-) strains TA100, TA98 and TA102. Isoquercitrin only slightly increased the number of revertants, while rutin was totally non-mutagenic. On the other hand, all compounds displayed dose-dependent protective activity against H2O2 - and tert-butyl hydroperoxide-induced oxidative damage to the TA102 strain and at 75 µmol L(-1) inhibited H2O2/Fe(2+)-induced formation of the open circular and linear forms of the DNA plasmid pBSIISK(-). In mice, none of the flavonols (0.86 µmol day(-1), 34 days) induced harmful effects. In immunized animals, all compounds enhanced ex vivo B cell proliferation; quercetin stimulated lymphocyte basal proliferation and increased the number of IgM-producing lymphocytes. Rutin promoted NK cytotoxic activity, supported T cells and enhanced gut epithelium renewal. No effect on IgG-forming cells was found. CONCLUSION: Isoquercitrin displayed negligible and rutin no mutagenicity, but both showed significant antimutagenic and DNA-protective effects against oxidative damage. In vivo, they supported the readiness of the immune system for specific humoral immune response.
- Klíčová slova
- (anti)mutagenicity, antibody formation, cytotoxic activity, lymphoid cell proliferation, mice, quercetin glycosides,
- MeSH
- aktivace lymfocytů účinky léků MeSH
- antimutagenní látky * MeSH
- dieta MeSH
- glykosidy farmakologie MeSH
- imunita účinky léků MeSH
- imunologické faktory * MeSH
- lidé MeSH
- mutageneze účinky léků MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- poškození DNA účinky léků MeSH
- quercetin analogy a deriváty farmakologie MeSH
- rutin farmakologie MeSH
- Salmonella typhimurium MeSH
- testy genotoxicity MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antimutagenní látky * MeSH
- glykosidy MeSH
- imunologické faktory * MeSH
- isoquercitrin MeSH Prohlížeč
- quercetin MeSH
- rutin MeSH
Concentrated extracts of MRS (De Man-Rogosa-Sharpe) media in which probiotic bacterium Enterococcus faecium strain M-74 was grown exerted different antimutagenic activity against ofloxacin-, N-methyl, N'-nitro-N-nitrosoguanidine- and sodium 5-nitro-2-furylacrylate-induced mutagenicity in Salmonella typhimurium assay depending on the presence (+Se) or absence of disodium selenite pentahydrate (-Se). The antimutagenicity of MRS(+Se) extract was higher than that of MRS(-Se) extract. Selenium enhanced also the antimutagenic effect of both live and killed cells of E. faecium M-74, respectively. The live bacteria decreased the mutagenicity of selected substances more than killed cells. Synergic activity of selenium with the bacterium was also manifested.
- MeSH
- antimutagenní látky farmakologie MeSH
- Enterococcus faecium metabolismus fyziologie MeSH
- mutageneze účinky léků MeSH
- mutageny toxicita MeSH
- probiotika farmakologie MeSH
- Salmonella typhimurium účinky léků genetika MeSH
- selen farmakologie MeSH
- synergismus léků MeSH
- testy genotoxicity MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antimutagenní látky MeSH
- mutageny MeSH
- selen MeSH
Total and fractionated organic extracts from industrial effluents and Labe river water were tested for mutagenicity using the Ames test with TA98 strain and its YG derivatives (YG1021, YG1024 and YG1041) and cytogenetic analysis with human peripheral lymphocytes in vitro. The bacterial mutagenicity results showed a dose-dependent increase in numbers of TA98 revertants (10(5)) with effluent extracts and lower, but still significant, increase (10(3)) with river water extracts 6 km downstream. The further increase of YG revertants indicates the possible presence of nitroarenes and aromatic amines in the tested samples. In fractionated samples the significant mutagenicity was detected in two-polar acidic and polar basic-fractions, but the numbers of revertants in all effluent fractions were about one order of magnitude lower compared with total extracts results. The cytogenetic effect in human peripheral lymphocytes in vitro was not significant. The increase in chromosomal aberrations was not clearly dose-dependent and may reflect more the combination of toxic and clastogenic effects.
- MeSH
- chemické látky znečišťující vodu škodlivé účinky analýza MeSH
- chromozomální aberace genetika MeSH
- kultivované buňky MeSH
- lidé MeSH
- lymfocyty účinky léků MeSH
- mutageneze účinky léků MeSH
- mutageny analýza MeSH
- průmyslový odpad škodlivé účinky analýza MeSH
- Salmonella typhimurium účinky léků genetika MeSH
- sladká voda analýza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chemické látky znečišťující vodu MeSH
- mutageny MeSH
- průmyslový odpad MeSH
The sensibility of the strain As-F2 Aspergillus fumigatus to EMS was determined by using the scale of doses. Seventeen thermo-sensitive or thermotolerant morphological mutants with decreased sporulation and growth rate as compared with a wild strain was isolated. Their more detailed characteristic will be a contents of our further paper.
The metabolic inhibitors acetaminophen, 7,8-benzoflavone, and methimazole significantly reduced the mutagenicity of the promutagen N-nitrosodimethylamine in the higher plant Arabidopsis thaliana. In contrast, these metabolic inhibitors had no effect on the mutagenicity of the direct-acting mutagen N-methyl-N'-nitro-N-nitrosoguanidine.
- MeSH
- antimutagenní látky farmakologie MeSH
- Arabidopsis účinky léků genetika MeSH
- benzoflavony farmakologie MeSH
- dimethylnitrosamin toxicita MeSH
- methimazol farmakologie MeSH
- mutageneze účinky léků MeSH
- mutageny toxicita MeSH
- paracetamol farmakologie MeSH
- semena rostlinná účinky léků genetika MeSH
- spektrofotometrie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alpha-naphthoflavone MeSH Prohlížeč
- antimutagenní látky MeSH
- benzoflavony MeSH
- dimethylnitrosamin MeSH
- methimazol MeSH
- mutageny MeSH
- paracetamol MeSH
- MeSH
- anthrachinony farmakologie MeSH
- antitumorózní látky farmakologie MeSH
- imunita účinky léků MeSH
- lidé MeSH
- mutageneze účinky léků MeSH
- nádory jater chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- anthrachinony MeSH
- antitumorózní látky MeSH
The non-selective actions of cytostatic drugs are responsible for both the required therapeutical effects and for some undesirable side effects on the human organism. The undesirable side effects are most hazardous to the occupationally exposed health personnel. This has led in a number of countries, including Czechoslovakia, to the elaboration of guidelines for the safe handling of cytostatic drugs. The occupational risk can be minimized by strict adherence to safety measures and the use of protective equipment of the workplace.
- MeSH
- antitumorózní látky škodlivé účinky MeSH
- lidé MeSH
- mutageneze účinky léků MeSH
- nádory chemicky indukované MeSH
- nemoci z povolání chemicky indukované MeSH
- zdravotničtí pracovníci * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antitumorózní látky MeSH
