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
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.
- 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
- MeSH
- antimutagenní látky farmakologie MeSH
- Enterococcus faecium účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- kultivační média speciální MeSH
- mutageneze účinky léků MeSH
- probiotika aplikace a dávkování MeSH
- Salmonella typhimurium účinky léků MeSH
- sloučeniny selenu farmakologie MeSH
- Publikační typ
- srovnávací studie MeSH
