Assessment of genotoxicity of vincristine, vinblastine and vinorelbine in human cultured lymphocytes: a comparative study

Abstract

Vincristine (VCR), vinblastine (VBL) and vinorelbine (VRL) are anticancer agents from the Vinca alkaloid family that have the potential to induce genotoxic effect. The aim of the present study was to compare the genotoxic effect of VCR, VBL and VRL. Levels of 8-hydroxy-2-deoxy guanosine (8-OHdG) and sister chromatid exchanges (SCEs) were measured in cultured human blood lymphocytes treated with VCR, VBL and VRL at concentrations of 0.01 and 0.1 μg/mL. Results showed that VCR, VBL and VRL significantly increased the 8-OHdG levels (p <0.05), whereas it did not cause a significant increase in the frequencies of SCEs in human blood lymphocytes as compared to controls. On the other hand, all three agents significantly increased cells mitotic index (p <0.05). At both tested concentrations, the magnitude of the increase in 8-OHdG was VBL>VCR>VRL. In conclusion, VCR, VBL and VRL induce DNA damage as indicated by the increase in the 8-OHdG biomarker but with different magnitude.

Potent antileukemic activity of curaxin CBL0137 against MLL‐rearranged leukemia

“…Although vincristine has been shown to induce DNA damage, our previous studies in neuroblastoma cells in vitro suggested that the enhanced cytotoxicity of vincristine by CBL0137 is not based on a CBL0137-induced inhibition of DNA damage repair. 14,50 This, however, does not preclude that it could be a mechanism of enhancement in leukemia cells and warrants future investigation. Alternatively, based on studies in glioblastoma and small-cell lung cancer, it can be hypothesized that enhancement between CBL0137 and the tested conventional treatment regimens is brought about by a preferential targeting of cancer stem cells by CBL0137, in complement to the actions of conventional chemotherapeutics that are thought to be poorly active against cancer stem cells.…”

Vitamin B12 protects against DNA damage induced by hydrochlorothiazide

“…After that, the slides were irradiated using a 350 mm UV lamp and two 15 W tubes lamps at a distance of 7 cm for 35 min at 40 °C. Finally, the slides were rinsed with distilled water, re-stained for 6–8 min with 5% Giemsa stain and then air dried (Khabour et al, 2014, Mhaidat et al, 2016).…”

Getting Lost in the Cell–Lysosomal Entrapment of Chemotherapeutics

“…Each of the Catharanthus derivatives, namely vinblastine, vincristine, and vindesine, exhibits varying capacity to inhibit net tubulin polymerization and mediate cytostasis [44]. Intriguingly, despite functioning as MT-targeting agents, vincristine, vinblastine, and vinorelbine can also induce extensive oxidative DNA damage [45].…”

“…Inhibits microtubule polymerization Induces oxidative DNA damage [43,45] Taxane Docetaxel, Paclitaxel Binds to and stabilizes tubulin polymers [140]…”