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Journal of Gastrointestinal Cancer

, Volume 49, Issue 2, pp 172–180 | Cite as

Opium Consumption and the Incidence of Cancer: Does Opium Account as an Emerging Risk Factor for Gastrointestinal Cancer?

  • Mohammed Azeez Alzaidi
  • Hossein Ali Arab
  • Saeid Amanpour
  • Reza Shirkoohi
  • Samad Muhammadnejad
  • Farhang Sasani
Original Research
  • 95 Downloads

Abstract

Purpose

Some epidemiological studies have shown an association between opium consumption and the incidence of gastrointestinal (GI) cancer. The present study was designed to investigate the effects of opium on the initiation of GI cancer in rats.

Methods

Forty-five rats were randomly divided into three groups; each received different treatment for 40 weeks. The rats in group 1 received purified water, while animals in group 2 were treated with 5 mg/kg diethylnitrosamine (DEN) orally for 8 weeks and continued with purified water by the end of the experiment. The third experimental group received 300 mg/kg opium for 16 weeks and then continued with 50 mg/kg phenobarbital by the end of the 40th week. The growth of tumors in the treated groups was assessed by histological changes and the up/down expression of p53, cdkn1, cdk2, e-cdh, and n-cdh genes in different parts of GI tract.

Results

Histological examinations revealed that DEN was able to induce the growth of tumor in GI tract as shown by active mitotic figure in different regions of GI system and hyperplasia of hepatocytes associated with infiltration of inflammatory cells, intestinal villous hypertrophy, and colorectal adenoma. There was also significant (p < 0.05) overexpression of p53, cdk2, and n-Cdh genes in different parts of digestive system in DEN-treated group. However, these pathological changes and the degradation of gene expression were not observed in the opium-treated group.

Conclusion

The results of this study suggest that the opium does not promote the initiation of cancer in GI tract.

Keywords

Diethylnitrosamine Opium Cancer Gastrointestinal tract 

Notes

Acknowledgements

We would like to thank the Ministry of Higher Education and Scientific Research in Iraq and the University of Tehran for funding this study. Special thanks to Dr. Hossein Golami and Dr. Hassan Khalaf Al-Qaraghouli for preparation of some pathological pictures of tissues.

Compliance with Ethical Standards

The experimental protocol has been approved by the institutional Animal care and use Committee.

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Sadjadi A, Nouraie M, Mohagheghi MA, Mousavi-Jarrahi A, Malekezadeh R, Parkin DM. Cancer occurrence in Iran in 2002, an international perspective. Asian Pac J Cancer Prev. 2005;6(3):359–63.PubMedGoogle Scholar
  2. 2.
    American Cancer Society. Cancer facts and figures. Atlanta, GA: Publisher American cancer Society. 2012. http://www.cancer.org/research/cancerfactfigures/cancer-facts-figure-2012:1-2.
  3. 3.
    Liao DJ, Blanck A, Eneroth P, Gustafsson JA, Hällström IP. Diethylnitrosamine causes pituitary damage, disturbs hormone levels, and reduces sexual dimorphism of certain liver functions in the rat. Environ Health Perspect. 2001;109(9):943–7.  https://doi.org/10.1289/ehp.01109943.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Verna L, Whysner J, Williams GM. N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation. Pharmacol Ther. 1996;71(1):57–81.  https://doi.org/10.1016/0163-7258(96)00062-9.CrossRefPubMedGoogle Scholar
  5. 5.
    Aggrawal A. Opium: the king of narcotics. In: Aggrawal A, editor. Narcotic drugs. New Delhi: New Delhi National Book Trust; 1995. p. 161.Google Scholar
  6. 6.
    United Nations Office on Drugs and Crime (UNODC). World drug report 2010. United Nations Publication Sales No.10.XI.13; 2010:1–50.Google Scholar
  7. 7.
    Heydari M, Hashem Hashempur M, Zargaran A. Medicinal aspects of opium as described in Avicenna’s Canon of Medicine. Acta Medico-Historica Adriatica. 2013;11(1):101–12.PubMedGoogle Scholar
  8. 8.
    Shakeri R, Kamangar F, Nasrollahzadeh D, Nouraie M, Khademi H, Etemadi A, et al. Is opium a real risk factor for esophageal cancer or just a methodological artifact? Hospital and neighborhood controls in case-control studies. PLoS One. 2012;7(3):e32711.  https://doi.org/10.1371/journal.pone.0032711.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Malekzadeh MM, Khademi H, Pourshams A, Etemadi A, Poustchi H, Bagheri M, et al. Opium use and risk of mortality from digestive diseases: a prospective cohort study. Am J Gastroenterol. 2013;108(11):1757–65.  https://doi.org/10.1038/ajg.2013.336.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Shakeri R, Malekzadeh R, Etemadi A, Nasrollahzadeh D, Aghcheli K, Sotoudeh M, et al. Opium: an emerging risk factor for gastric adenocarcinoma. Int J Cancer. 2013;133(2):455–61.  https://doi.org/10.1002/ijc.28018.CrossRefPubMedGoogle Scholar
  11. 11.
    Mousavi MRA, Damghani MA, Haghdoust AA, Khamesipour A. Opium and risk of laryngeal cancer. Laryngoscope. 2003;113(11):1939–43.CrossRefPubMedGoogle Scholar
  12. 12.
    Khademi H, Malekzadeh R, Pourshams A, Jafari E, Salahi R, Semnani S, et al. Opium use and mortality in Golestan Cohort Study: prospective cohort study of 50 000 adults in Iran. BMJ. 2012;344(apr17 2):e2502.  https://doi.org/10.1136/bmj.e2502.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Hosseini SY, Safarinejad MR, Amini E, Hooshyar H. Opium consumption and risk of bladder cancer: a case-control analysis. In: Urologic Oncology: Seminars and Original Investigations. Elsevier; 2010. vol 6, p. 610–616.Google Scholar
  14. 14.
    Dillenburg CF, Kruel CDP, Cerski CT, Edelweiss MI, Schier AS. Morphine does no promote esophageal carcinogenesis in rats exposed to diethylnitrosamine. Arq Gastroenterol. 2008;45(1):87–92.  https://doi.org/10.1590/S0004-28032008000100016.CrossRefPubMedGoogle Scholar
  15. 15.
    Tegeder I, Grösch S, Schmidtko A, Häussler A, Schmidt H, Niederberger E, et al. G protein-independent G1 cell cycle block and apoptosis with morphine in adenocarcinoma cells. Cancer Res. 2003;63(8):1846–52.PubMedGoogle Scholar
  16. 16.
    Sasamura T, Nakamura S, Iida Y, Fujii H, Murata J, Saiki I, et al. Morphine analgesia suppresses tumor growth and metastasis in a mouse model of cancer pain produced by orthotopic tumor inoculation. Eur J Pharmacol. 2002;441(3):185–91.  https://doi.org/10.1016/S0014-2999(02)01450-4.CrossRefPubMedGoogle Scholar
  17. 17.
    Aneja R, Zhou J, Zhou B, Chandra R, Joshi HC. Treatment of hormone-refractory breast cancer: apoptosis and regression of human tumors implanted in mice. Mol Cancer Ther. 2006;5(9):2366–77.  https://doi.org/10.1158/1535-7163.MCT-06-0205.CrossRefPubMedGoogle Scholar
  18. 18.
    Jackson T, Chougule MB, Ichite N, Patlolla RR, Singh M. Antitumor activity of noscapine in human non-small cell lung cancer xenograft model. Cancer Chemother Pharmacol. 2008;63(1):117–26.  https://doi.org/10.1007/s00280-008-0720-z.CrossRefPubMedGoogle Scholar
  19. 19.
    Aneja R, Ghaleb AM, Zhou J, Yang VW, Joshi HC. p53 and p21 determine the sensitivity of noscapine-induced apoptosis in colon cancer cells. Cancer Res. 2008;67(8):3862–70.CrossRefGoogle Scholar
  20. 20.
    Sajadian S, Vatankhah M, Majdzadeh M, Kouhsari SM, Ghahremani MH, Ostad SN. Cell cycle arrest and apoptogenic properties of opium alkaloids noscapine and papaverine on breast cancer stem cells. Toxicol Mech Methods. 2015;25(5):388–95.  https://doi.org/10.3109/15376516.2015.1045656.CrossRefPubMedGoogle Scholar
  21. 21.
    Hayes AW, Kruger CL. Hayes’ principles and methods of toxicology. Boca Raton: CRC Press; 2014.Google Scholar
  22. 22.
    Lijinsky W. Chemistry and biology of N-nitroso compounds. Cambridge: Cambridge University Press; 1992.Google Scholar
  23. 23.
    Sánchez-Pérez Y, Carrasco-Legleu C, García-Cuellar C, Pérez-Carreón J, Hernández-García S, Salcido-Neyoy M, et al. Oxidative stress in carcinogenesis. Correlation between lipid peroxidation and induction of preneoplastic lesions in rat hepatocarcinogenesis. Cancer Lett. 2005;217(1):25–32.  https://doi.org/10.1016/j.canlet.2004.07.019.CrossRefPubMedGoogle Scholar
  24. 24.
    Schmahl D. Combination effects in chemical carcinogenesis. In: Chambers PL, Klinger W, editors. Further studies in the assessment of toxic actions. Arch Toxicol Suppl. 1980;4:29–40.Google Scholar
  25. 25.
    Lijinsky W. Intestinal cancer induced by N-nitroso compounds. Toxicol Pathol. 1988;16(2):198–204.  https://doi.org/10.1177/019262338801600212.CrossRefPubMedGoogle Scholar
  26. 26.
    Kawanishi S, Hiraku Y, Murata M, Oikawa S. The role of metals in site-specific DNA damage with reference to carcinogenesis 1, 2. Free Radic Biol Med. 2002;32(9):822–32.  https://doi.org/10.1016/S0891-5849(02)00779-7.CrossRefPubMedGoogle Scholar
  27. 27.
    Valko M, Rhodes C, Moncol J, Izakovic M, Mazur M. Free radicals, metals and antioxidants in oxidative stress-induced cancer. Chem Biol Interact. 2006;160(1):1–40.  https://doi.org/10.1016/j.cbi.2005.12.009.CrossRefPubMedGoogle Scholar
  28. 28.
    Pawan M, Choudhary R, Mathur R, Choudhary M, Kamla M. Study on harmful effects of opium on liver and lungs in chronic opium addicts of western Rajasthan. Journal of Bangladesh Society of Physiologist. 2011;6(2):122–6.Google Scholar
  29. 29.
    Atici S, Cinel I, Cinel L, Doruk N, Eskandari G, Oral U. Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model. J Biosci. 2005;30(2):245–52.  https://doi.org/10.1007/BF02703705.CrossRefPubMedGoogle Scholar
  30. 30.
    Frenklakh L, Bhat RS, Bhaskaran M, Sharma S, Sharma M, Dinda A, et al. Morphine-induced degradation of the host defense barrier. Dig Dis Sci. 2006;51(2):318–25.  https://doi.org/10.1007/s10620-006-3132-0.CrossRefPubMedGoogle Scholar
  31. 31.
    Harari Y, Weisbrodt NW, Moody FG. The effect of morphine on mast cell–mediated mucosal permeability. Surgery. 2006;139(1):54–60.  https://doi.org/10.1016/j.surg.2005.07.009.CrossRefPubMedGoogle Scholar
  32. 32.
    Aylon Y, Oren M. New plays in the p53 theater. Curr Opin Genet Dev. 2011;21(1):86–92.  https://doi.org/10.1016/j.gde.2010.10.002.CrossRefPubMedGoogle Scholar
  33. 33.
    El-Deiry W. P21/P53, cellular growth control and genomic integrity. Cyclin Dependent Kinase (CDK) Inhibitors. In: Current Topics in Microbiology and Immunology book series. 1998;227:121–137.Google Scholar
  34. 34.
    Abbas T, Dutta A. p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer. 2009;9(6):400–14.  https://doi.org/10.1038/nrc2657.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Zhu W, Abbas T, Dutta A. DNA Replication and Genomic. Genomic Advances in Experimental Medicine and Biology book series. 2005; 249–279.Google Scholar
  36. 36.
    Pasz-Walczak G, Kordek R, Faflik M. P21 (WAF1) expression in colorectal cancer: correlation with P53 and cyclin D1 expression, clinicopathological parameters and prognosis. Pathology-Research and Practice. 2001;197(10):683–9.  https://doi.org/10.1078/0344-0338-00146.CrossRefGoogle Scholar
  37. 37.
    Sotillo R, Dubus P, Martn J, de la Cueva E, Ortega S, Malumbres M, et al. Wide spectrum of tumors in knock-in mice carrying a Cdk4 protein insensitive to INK4 inhibitors. EMBO J. 2001;20(23):6637–47.  https://doi.org/10.1093/emboj/20.23.6637.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Doak S, Jenkins G, Parry E, Griffiths A, Shah V, Baxter J, et al. Characterisation of p53 status at the gene, chromosomal and protein levels in oesophageal adenocarcinoma. Br J Cancer. 2003;89(9):1729–35.  https://doi.org/10.1038/sj.bjc.6601323.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018
corrected publication March/2018

Authors and Affiliations

  • Mohammed Azeez Alzaidi
    • 1
  • Hossein Ali Arab
    • 1
  • Saeid Amanpour
    • 2
  • Reza Shirkoohi
    • 2
  • Samad Muhammadnejad
    • 2
  • Farhang Sasani
    • 3
  1. 1.Department of Pharmacology, Faculty of Veterinary MedicineUniversity of TehranTehranIran
  2. 2.Cancer Biology Research CenterTehran University of Medical SciencesTehranIran
  3. 3.Department of Pathology, Faculty of Veterinary MedicineUniversity of TehranTehranIran

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