ASSESSMENT OF GENOTOXICITY OF VINCRISTINE, VINBLASTINE AND VINORELBINE IN HUMAN CULTURED LYMPHOCYTES: A COMPARATIVE STUDY
Mhaidat NM, Alzoubi KH, Khabour OF, Alawneh KZ, Raffee LA, Alsatari ES, Hussein EI, Bani-Hani KE
*Corresponding Author: Nizar M. Mhaidat, Ph.D., Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Amman-Ramtha Hwy, Irbid 22110, Jordan. Tel: +962- 2-720-100. Fax: +962-2-720-1075. E-mail: nizarm@just.edu.jo
page: 13
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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.



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