Document Type : Original Article


1 Cancer Bioengineering Laboratory, Faculty of Nature and Life Sciences, University of Bejaia, Algeria

2 Cancer Bioengineering Laboratory, Faculty of Medicine, University of Bejaia, Algeria


Background: In this study, we suggested an experimental procedure demonstrating the impact of pesticide on the development of ectopic xenografts of human glioblastomas in immuno-competent Balb/c mice.
Method: In this in-vivo study, the mice were treated with or without a mixture of pesticide (Glyphosate and Chlorpyrifos), using a concentration corresponding to 1/8 of LD50 of each pesticide. The pesticides were injected intraperitoneally every 72 hours. The human glioblastoma cell suspension was cultured with tumor cerebrospinal fluid and then injected subcutaneously into the treated and not treated mice with a mixture of pesticide (Glyphosate and Chlorpyrifos) following 18 days after the beginning of the experiment.
Results: The body mass index of the male and female mice treated with pesticide was statistically (P = 0.0048) higher than those not treated with pesticides. 66.6% of the mice treated with pesticides and xenografts of glioblastoma developed masses at the injection site. The histological analysis revealed that 41.66% of the masses were astrocytic tumors. The other found masses corresponded to inflammatory lymph nodes and fibroblastic tissue formations.
Conclusion: The treatment of mice with pesticide mixture was found to allow the development of glioblastoma xenografts in immunocompetent mice.


How to cite this article:

Ghidouche A, Tliba S, Ait-Ali D. Establishment of ectopic xenografts derived from human glioblastoma in immunocompetent mouse model treated with pesticide. Middle East J Cancer. 2022;13(3):384-92. doi: 10.30476/mejc.2021.87541.1436.

  1. Bray F, Ferlay J, Laversanne M, Brewster DH, GombeMbalawa C, Kohler B, et al. Cancer incidence in five continents: Inclusion criteria, highlights from volume X and the global status of cancer registration. Int J Cancer.2015;137:2060-71. doi: 10.1002/ijc.29670.
  2. Ostrom QT, Gittleman H, Kruchko C, Louis DN, Brat DJ, Gilbert MR, et al. Completeness of required site-specific factors for brain and CNS tumors in the Surveillance, Epidemiology and End Results (SEER) 18 database (2004-2012, varying). J Neurooncol. 2016. doi: 10.1007/s11060-016-2217-7.
  3. Quach P, El Sherif R, Gomes J, Krewksi D. A systematic review of the risk factors associated with the onset and progression of primary brain tumours. Neurotoxicology. 2016. doi: 10.1016/j.neuro.2016.05.009.
  4. Kunkle B, Bae S, Singh KP, Roy D. Increased risk of childhood brain tumors among children whose parents had farm-related pesticide exposures during pregnancy. JP J Biostat. 2014;11:89-101.
  5. Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. ActaNeuropathol (Berl).2016;131:803-20. doi: 10.1007/s00401-016-1545-1.
  6. Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M. Epidemiology and molecular pathology of glioma. Nat ClinPract Neurol. 2006;2:494-503. doi:10.1038/ncpneuro0289.
  7. Xie Q, Mittal S, Berens ME. Targeting adaptive glioblastoma: an overview of proliferation and invasion.Neuro-Oncol. 2014;16:1575-84. doi:10.1093/neuonc/nou147.
  8. Cheon DJ, Orsulic S. Mouse models of cancer. Annu Rev PatholMech Dis. 2011;6:95-119. doi:10.1146/annurev.pathol.3.121806.154244.
  9. Jung J. Human tumor xenograft models for preclinical assessment of anticancer drug development. Toxicol Res. 2014;30:1-5. doi:10.5487/TR.2014.30.1.001.
  10. Irtenkauf SM, Sobiechowski S, Hasselbach LA, Nelson KK, Transou AD, Carlton ET, et al. Optimization of glioblastoma mouse orthotopicxenograft models for translational research. Comp Med. 2017;67:300-14.
  11. Huszthy PC, Daphu I, Niclou SP, Stieber D, Nigro JM, Sakariassen PO, et al. In vivo models of primary brain tumors: pitfalls and perspectives. Neuro-Oncol. 2012;14:979-93. doi:10.1093/neuonc/nos135.
  12. Akbasak A, Toevs CC, Laske DW. Reconstituted basement membrane (matrigel) enhances the growth of human glioma cell lines in nude mice. J Neurooncol. 1996;27:23-30.
  13. Kim KM, Shim JK, Chang JH, Lee JH, Kim SH, Choi J, et al. Failure of a patient-derived xenograft for brain tumor model prepared by implantation of tissue fragments. Cancer Cell Int. 2016;16. doi:10.1186/s12935-016-0319-0.
  14. Sudjaroen Y. Biochemical and hematological status of pesticide sprayers in SamutSongkhram, Thailand. Ann Trop Med Public Health. 2015;8:186. doi:10.4103/1755-6783.159843.
  15. Aroonvilairat S, Kespichayawattana W, Sornprachum T, Chaisuriya P, Siwadune T, Ratanabanangkoon K. Effect of pesticide exposure on immunological, hematological and biochemical parameters in Thai orchid farmers— A cross-sectional study. Int J Environ Res Public Health. 2015;12:5846-61. doi:10.3390/ijerph120605846.
  16. Keifer MC, Firestone J. Neurotoxicity of pesticides. J Agromedicine. 2007;12:17-25. doi:10.1300/J096v12n01_03.
  17. Magnarelli G, Fonovich T. Protein phosphorylation pathways disruption by pesticides. AdvBiol Chem.2013;03:460-74. doi:10.4236/abc.2013.35050.
  18. Van Maele-Fabry G, Gamet-Payrastre L, Lison D. Residential exposure to pesticides as risk factor for childhood and young adult brain tumors: A systematic review and meta-analysis. Environ Int. 2017;106:69-90. doi: 10.1016/j.envint.2017.05.018.
  19. Reed A, Dzon L, Loganathan BG, Whalen MM. Immunomodulation of human natural killer cell cytotoxic function by organochlorine pesticides. Hum ExpToxicol. 2004;23:463-71. doi:10.1191/0960327104ht477oa.
  20. Díaz-Resendiz KJG, Toledo-Ibarra GA, Girón-Pérez MI. Modulation of immune response by organophosphorus pesticides: fishes as a potential model in immunotoxicology. J Immunol Res. 2015;2015:213836. doi:10.1155/2015/213836.
  21. Sakka L, Coll G, Chazal J. Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis. 2011;128:309-16. doi:10.1016/j.anorl.2011.03.002.
  22. Abbott NJ. Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int.2004;45:545-52. doi:10.1016/j.neuint.2003.11.006.