Mequindox (MEQ) is a synthetic antibacterial agent. Recent studies showed that MEQ and its primary metabolites exhibit strong genotoxicity to mammalian cells, and MEQ induced carcinogenicity in mice. These findings suggest that chronic exposure to MEQ could lead to an increased risk of cancer later in life. In the present study, four groups of Wistar rats (55 rats/sex/group) were fed with diets containing MEQ (0, 25, 55, and 110 mg/kg) for 2 years. The results showed that the hematological system, liver, kidneys, and adrenal glands, as well as the developmental and reproductive systems, were the main targets for MEQ. Liver toxicity mediated by MEQ was associated with apoptosis and the nuclear factor κB (NF-κB) signaling pathway. In addition, MEQ increased the incidence of tumors in rats. Phosphorylated histone H2AX (γ-H2AX) is identified as a biomarker of cellular response to DNA double-strand breaks (DSB). Our data demonstrated that γ-H2AX expression was significantly increased in tumors. Thus, high levels of DSB might be responsible for carcinogenesis in rats, and further investigation is absolutely required to clarify the exact molecular mechanisms for carcinogenicity caused by MEQ in vivo.
- MeSH
- analýza přežití MeSH
- apoptóza účinky léků MeSH
- chinoxaliny toxicita MeSH
- dietární expozice MeSH
- experimentální nádory metabolismus MeSH
- fosfoproteiny biosyntéza MeSH
- histony biosyntéza MeSH
- imunohistochemie MeSH
- játra účinky léků metabolismus MeSH
- karcinogeny toxicita MeSH
- NF-kappa B metabolismus MeSH
- poškození DNA * MeSH
- potkani Wistar MeSH
- tělesná hmotnost účinky léků MeSH
- velikost orgánu účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
