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

INTRODUCTION

Vinca alkaloids are a subset of drugs derived from the Madagascar periwinkle plant (Catharanthus roseus) [1]. They include the natural products vincristine (VCR) and vinblastine (VBL) and the semi-synthetic derivative vin-orelbine (VRL). Vinca alkaloids have been used for cancer management [2]. Chemically, vinca alkaloids have dimeric chemical structures composed of two basic multi-ringed units, an indole nucleus (catharanthine) and a dihydroindole nucleus (vindoline), joined together with other complex systems [2,3]. Different Vinca alkaloids have their own unique properties. The VBL inhibits angiogenesis [4]. It is also associated with anti-diuretic hormone secretion and angina, and applied to treat Hodgkin’s disease, non-Hodgkin’s lymphoma and breast cancer [5]. The VRL showed a significant anti-tumor activity in patients with breast cancer and induces anti-proliferative activity in osteosarcoma [6]. Moreover, VCR has been shown to have a mild myelo-suppressive action [7,8]. It is also widely used to treat pediatric leukemias, solid tumors, and hematological malignancies [2]. During cell division, Vinca alkaloids bind to the building blocks of a protein called tubulin, inhibiting its formation, which normally works in cells to create mitotic spindle [9]. Previous studies have shown that Vinca alkaloids have the potential to induce genotoxic effects in different biological systems. The VCR and VBL have been shown to increase the frequency of micronuclei in experimental animals and in cultured human lymphocytes [10-13]. In addition, they have also been shown to cause chromosomal mutations in vivo and in cultured cancer cells [14,15]. In cultured human lymphocytes, VRB and VCR increased the rate of micronucleus formation [16]. In Drosophila, VCR and VBL induced a significant genotoxic effect as measured using wing somatic mutation and the recombination test [17]. However, some other studies have shown lack of mutagenic effect for Vinca alkaloids in vivo and in cultured cells [18-20]. Thus, the genotoxicity of Vinca alkaloids is still controversial. In addition, oxidative DNA damage induced by these compounds has still not been investigated. The aim of the present study was to compare the genotoxic effect of VCR, VBL and VRL on human cultured lymphocytes using 8-hydroxy-2-deoxy guanosine (8-OHdG) and sister chromatid exchanges (SCEs) assays. The 8-OHdG is a marker that reflects oxidative DNA damage, while the SCEs assay reflects genotoxicity induced as a result of breaks in DNA during DNA recombination.



Number 26
Number 26 VOL. 26(2), 2023 All in one
Number 26
VOL. 26(2), 2023
Number 26
VOL. 26, 2023 Supplement
Number 26
VOL. 26(1), 2023
Number 25
VOL. 25(2), 2022
Number 25
VOL. 25 (1), 2022
Number 24
VOL. 24(2), 2021
Number 24
VOL. 24(1), 2021
Number 23
VOL. 23(2), 2020
Number 22
VOL. 22(2), 2019
Number 22
VOL. 22(1), 2019
Number 22
VOL. 22, 2019 Supplement
Number 21
VOL. 21(2), 2018
Number 21
VOL. 21 (1), 2018
Number 21
VOL. 21, 2018 Supplement
Number 20
VOL. 20 (2), 2017
Number 20
VOL. 20 (1), 2017
Number 19
VOL. 19 (2), 2016
Number 19
VOL. 19 (1), 2016
Number 18
VOL. 18 (2), 2015
Number 18
VOL. 18 (1), 2015
Number 17
VOL. 17 (2), 2014
Number 17
VOL. 17 (1), 2014
Number 16
VOL. 16 (2), 2013
Number 16
VOL. 16 (1), 2013
Number 15
VOL. 15 (2), 2012
Number 15
VOL. 15, 2012 Supplement
Number 15
Vol. 15 (1), 2012
Number 14
14 - Vol. 14 (2), 2011
Number 14
The 9th Balkan Congress of Medical Genetics
Number 14
14 - Vol. 14 (1), 2011
Number 13
Vol. 13 (2), 2010
Number 13
Vol.13 (1), 2010
Number 12
Vol.12 (2), 2009
Number 12
Vol.12 (1), 2009
Number 11
Vol.11 (2),2008
Number 11
Vol.11 (1),2008
Number 10
Vol.10 (2), 2007
Number 10
10 (1),2007
Number 9
1&2, 2006
Number 9
3&4, 2006
Number 8
1&2, 2005
Number 8
3&4, 2004
Number 7
1&2, 2004
Number 6
3&4, 2003
Number 6
1&2, 2003
Number 5
3&4, 2002
Number 5
1&2, 2002
Number 4
Vol.3 (4), 2000
Number 4
Vol.2 (4), 1999
Number 4
Vol.1 (4), 1998
Number 4
3&4, 2001
Number 4
1&2, 2001
Number 3
Vol.3 (3), 2000
Number 3
Vol.2 (3), 1999
Number 3
Vol.1 (3), 1998
Number 2
Vol.3(2), 2000
Number 2
Vol.1 (2), 1998
Number 2
Vol.2 (2), 1999
Number 1
Vol.3 (1), 2000
Number 1
Vol.2 (1), 1999
Number 1
Vol.1 (1), 1998

 

 


 About the journal ::: Editorial ::: Subscription ::: Information for authors ::: Contact
 Copyright © Balkan Journal of Medical Genetics 2006