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

doi:10.1515/bjmg-2016-0002

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.

References

Facchini PJ, De Luca V. Opium poppy and Madagascar periwinkle: Model non-model systems to investigate alkaloid biosynthesis in plants. Plant J. 2008; 54(4): 763-784.
Search in Google Scholar Back to article
Moudi MR, Go R, Yien CY, Nazre M. Vinca alkaloids. Int J Prev Med. 2013; 4(11): 1231-1235.
Search in Google Scholar Back to article
Duffin J. Poisoning the spindle: Serendipity and discovery of the anti-tumor properties of the Vinca alkaloids. Pharm Hist. 2002; 44(2?): 64-76.
Search in Google Scholar Back to article
Ribatti D, Guidolin D, Conconi MT, Nico B, Baiguera S, Parnigotto PP, et al. Vinblastine inhibits the angiogenic response induced by adrenomedullin in vitro and in vivo. Oncogene. 2003; 22(41): 6458-6461.
Search in Google Scholar Back to article
Toussaint C, Izzo J, Spielmann M, Merle S, May-Levin F, Armand JP, et al. Phase I/II trial of continuous infusion vinorelbine for advanced breast cancer. J Clin Oncol. 1994; 12(10): 2102-2112.
Search in Google Scholar Back to article
Freyer G, Delozier T, Lichinister M, Gedouin D, Bougnoux P, His P, et al. Phase II study of oral vinorelbine in first-line advanced breast cancer chemotherapy. J Clin Oncol. 2003; 21(1): 35-40.
Search in Google Scholar Back to article
Rusthoven J, Bramwell V, Stephenson B. Use of granulocyte colony-stimulating factor (G-CSF) in patients receiving myelosuppressive chemotherapy for the treatment of cancer. Provincial Systemic Treatment Disease Site Group. Cancer Prev Control. 1998; 2(4): 179-190.
Search in Google Scholar Back to article
Hirano M, Okamoto M, Maruyama F, Ezaki K, Shimizu K, Ino T, et al. Alternating non-crossresistant chemotherapy for non-Hodgkin’s lymphoma of inter-mediate-grade and high-grade malignancy. A pilot study. Cancer. 1992; 69(3): 772-777.
Search in Google Scholar Back to article
Coderch C, Morreale A, Gago F. Tubulin-based structure-affinity relationships for antimitotic Vinca alkaloids. Anticancer Agents Med Chem. 2012; 12(3): 219-225.
Search in Google Scholar Back to article
Jiang W, Lu Y, Chen Z, Chen S, Zhang M, Jin L, et al. Studying the genotoxicity of vincristine on human lymphocytes using comet assay, micronucleus assay and TCR gene mutation test in vitro. Toxicology. 2008; 252(1-3): 113-117.
Search in Google Scholar Back to article
Choudhury RC, Palo AK, Padhy A. Cytogenetic consequences of vinblastine treatment in mouse bone marrow. Chemotherapy. 2004; 50(4): 171-177.
Search in Google Scholar Back to article
Morales-Ramirez P, Vallarino-Kelly T, Cruz-Vallejo V. Kinetics of micronucleus induction and cytotoxicity caused by distinct antineoplastics and alkylating agents in vivo. Toxicol Lett. 2014; 224(3): 319-325.
Search in Google Scholar Back to article
Morales-Ramirez P, Vallarino-Kelly T, Cruz-Vallejo V. Kinetics of micronucleated polychromatic erythrocyte (MN-PCE) induction in vivo by aneuploidogens. Mutat Res. 2004; 565(1): 79-87.
Search in Google Scholar Back to article
Yamada T, Odawara K, Kaneko H. Concurrent detection of gene mutations and chromosome aberrations induced by five chemicals in a CHL/IU cell line incorporating a gpt shuttle vector. Mutat Res. 2000; 471(1-2): 29-36.
Search in Google Scholar Back to article
Arni P, Hertner T. Chromosomal aberrations in vitro induced by aneugens. Mutat Res. 1997; 379(1): 83-93.
Search in Google Scholar Back to article
Gonzalez-Cid M, Larripa I, Slavutsky I. Vinorelbine: Cell cycle kinetics and differential sensitivity of human lymphocyte subpopulations. Toxicol Lett. 1997; 93(2-3): 171-176.
Search in Google Scholar Back to article
Tiburi M, Reguly ML, Schwartsmann G, Cunha KS, Lehmann M, Rodrigues de Andrade HH. Comparative genotoxic effect of vincristine, vinblastine, and vinorelbine in somatic cells of Drosophila melanogaster. Mutat Res. 2002; 519(1-2): 141-149.
Search in Google Scholar Back to article
Gundy S, Baki M, Bodrogi I. Vinblastine, cisplatin and bleomycin (VPB) adjuvant therapy does not induce dose-dependent damage in human chromosomes. Neoplasma. 1989; 36(4): 457-464.
Search in Google Scholar Back to article
Morgan WF, Crossen PE. A comparison of induced sister chromatid exchange levels in Chinese hamster ovary cells and cultured human lymphocytes. Environ Mutagen. 1982; 4(1): 65-71.
Search in Google Scholar Back to article
Gonzalez-Cid M, Cuello MT, Larripa I. Mitotic arrest and anaphase aberrations induced by vinorelbine in hamster cells in vitro. Anticancer Drugs. 1997; 8(5): 529-532.
Search in Google Scholar Back to article
Alzoubi K, Khabour O, Khader M, Mhaidat N, Al-Azzam S. Evaluation of vitamin B12 effects on DNA damage induced by paclitaxel. Drug Chem Toxicol. 2014; 37(3): 276-280.
Search in Google Scholar Back to article
Alzoubi K, Khabour O, Hussain N, Al-Azzam S, Mhaidat M. Evaluation of vitamin B12 effects on DNA damage induced by pioglitazone. Mutat Res. 2012; 748(1-2): 48-51.
Search in Google Scholar Back to article
Alsatari ES, Azab M, Khabour OF, Alzoubi KH, Sadiq MF. Assessment of DNA damage using chromosomal aberrations assay in lymphocytes of waterpipe smokers. Int J Occup Med Environ Health. 2012; 25(3): 218-224.
Search in Google Scholar Back to article
Khabour OF, Alsatari ES, Azab M, Alzoubi KH, Sadiq MF. Assessment of genotoxicity of waterpipe and cigarette smoking in lymphocytes using the sister-chromatid exchange assay: A comparative study. Environ Mol Mutagen. 2011; 52(3): 224-228.
Search in Google Scholar Back to article
Alzoubi KH, Khabour OF, Jaber AG, Al-Azzam SI, Mhaidat NM, Masadeh MM. Tempol prevents geno-toxicity induced by vorinostat: role of oxidative DNA damage. Cytotechnology. 2014; 66(3): 449-455.
Search in Google Scholar Back to article
Khabour OF, Alzoubi KH, Mfady DS, Alasseiri M, Hasheesh TF. Tempol protects human lymphocytes from genotoxicity induced by cisplatin. Int J Clin Exp Med. 2014; 7(4): 982-988.
Search in Google Scholar Back to article
Al-Sweedan SA, Khabour O, Isam R. Genotoxicity assessment in patients with thalassemia minor. Mutat Res. 2012; 744(2): 167-171.
Search in Google Scholar Back to article
Kaya FF, Topaktas M. Genotoxic effects of potassium bromate on human peripheral lymphocytes in vitro. Mutat Res. 2007; 626(1-2): 48-52.
Search in Google Scholar Back to article
M’Bemba-Meka P, Lemieux N, Chakrabarti SK. Role of oxidative stress and intracellular calcium in nickel carbonate hydroxide-induced sister-chromatid exchange, and alterations in replication index and mitotic index in cultured human peripheral blood lymphocytes. Arch Toxicol. 2007; 81(2): 89-99.
Search in Google Scholar Back to article
Rooney DE, Ed. Human Cytogenetics. A Practical Approach, 3rd ed., Vol. 2: Malignancy and Acquired Abnormalities. Oxford, UK: Oxford University Press, 2001.
Search in Google Scholar Back to article
Khabour OF, Saleh N, Alzoubi KH, Hisaindee S, Al-Fyad D, Al-Kaabi L, et al. Genotoxicity of structurally related copper and zinc containing Schiff base complexes. Drug Chem Toxicol. 2013; 36(4): 435-442.
Search in Google Scholar Back to article
Ivett JL, Tice RR. Average generation time: A new method of analysis and quantitation of cellular proliferation kinetics. Environ Mutagen. 1982; 4: 358-370.
Search in Google Scholar Back to article
Tsai KL, Chiu TH, Tsai MH, Chen HY, Ou HC. Vinorelbine-induced oxidative injury in human endothelial cells mediated by AMPK/PKC/NADPH/NF-kappaB pathways. Cell Biochem Biophys. 2012; 62(3): 467-479.
Search in Google Scholar Back to article
Zhao J, Li H, Zhai Q, Qiu Y, Niu Y, Dai Y, et al. [Endonuclease modified comet assay for oxidative DNA damage induced by detection of genetic toxicants]. Zhonghua Yu Fang Yi Xue Za Zhi. 2014; 48(3): 208-212.
Search in Google Scholar Back to article
Madhu P, Reddy KP, Reddy PS. Melatonin reduces oxidative stress and restores mitochondrial function in the liver of rats exposed to chemotherapeutics. J Exp Zool A Ecol Genet Physiol. 2015; 323(5): 301-308.
Search in Google Scholar Back to article
Lee-Chen SF, Chen CL, Ho LY, Hsu PC, Chang JT, Sun CM, et al. Role of oxidative DNA damage in hydroxychavicol-induced genotoxicity. Mutagenesis. 1996; 11(5): 519-523.
Search in Google Scholar Back to article
Ogura H, Takeuchi T, Morimoto K. A comparison of the 8-hydroxydeoxyguanosine, chromosome aberrations and micronucleus techniques for the assessment of the genotoxicity of mercury compounds in human blood lymphocytes. Mutat Res. 1996; 340(2-3): 175-182.
Search in Google Scholar Back to article
Tari C, Fournier N, Briand C, Ducet G, Crevat A. Action of vinca alkaloides on calcium movements through mitochondrial membrane. Pharmacol Res Commun. 1986; 18(6): 519-528.
Search in Google Scholar Back to article
Sanchez P, Llorente MT, Castano A. Flow cytometric detection of micronuclei and cell cycle alterations in fish-derived cells after exposure to three model genotoxic agents: Mitomycin C, vincristine sulfate and benzo(a) pyrene. Mutat Res. 2000; 465(1-2): 113-122.
Search in Google Scholar Back to article
Le Fevre AC, Boitier E, Marchandeau JP, Sarasin A, Thybaud V. Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat Res. 2007; 619(1-2): 16-29.
Search in Google Scholar Back to article
Geriyol P, Basavanneppa HP, Dhananjaya BL. Protecting effect of caffeine against vinblastine (an anticancer drug) induced genotoxicity in mice. Drug Chem Toxicol. 2015; 38(2): 188-195.
Search in Google Scholar Back to article
Wang YJ, Zhang LS. [Evaluation of the genotoxicity of vincristine and colchicine using mouse lymphoma tk mutation assay]. Wei Sheng Yan Jiu. 2006; 35(2): 179-181.
Search in Google Scholar Back to article
Choudhury RC, Das B, Misra S, Jagdale MB. Cytogenetic toxicity of vincristine. J Environ Pathol Toxicol Oncol. 2000; 19(4): 347-355.
Search in Google Scholar Back to article
Xing SG, Shi X, Wu ZL, Chen JK, Wallace W, Whong WZ, et al. Transplacental genotoxicity of triethyl-enemelamine, benzene, and vinblastine in mice. Teratog Carcinog Mutagen. 1992; 12(5): 223-230.
Search in Google Scholar Back to article
Novichkova EA, Onishchenko GE, Shtil AA. Microtubule depolymerization by vincristine causes cell death after transition from C mitosis to interphase. Dokl Biol Sci. 2003; 393: 575-578.
Search in Google Scholar Back to article
Horton JK, Houghton PJ, Houghton JA. Relationships between tumor responsiveness, vincristine pharmacokinetics and arrest of mitosis in human tumor xenografts. Biochem Pharmacol. 1988; 37(20): 3995-4000.
Search in Google Scholar Back to article

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

Abstract

Paradigm

My account