Skip to main content
Log in

Zinc mediated normalization of histoarchitecture and antioxidant status offers protection against initiation of experimental carcinogenesis

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The present study evaluated the inhibitory effects of zinc on colonic antioxidant defense system and histoarchitecture during 1,2 dimethylhydrazine (DMH) induced colon carcinogenesis in male Sparque Dawley rats. The rats were segregated into four groups viz., normal control, DMH treated, zinc treated, DMH + zinc treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 8 weeks. Zinc (in the form of zinc sulphate) was supplemented to rats at a dose level of 227 mg/l in drinking water, ad libitum for the entire duration of the study. Increased lipid peroxidation was accompanied by a decrease in reduced glutathione (GSH), glutathione reductase (GR), glutathione-s-transferase (GST), superoxide dismutase (SOD), and catalase. Administration of zinc to DMH treated rats significantly decreased the lipid peroxidation levels with simultaneous enhancement of GSH, GR, GST, SOD, and Catalase. Histopathological studies from DMH treated rats revealed disorganization of colonic histoarchitecture. However, zinc treatment to DMH treated rats greatly restored normalcy in the colonic histoarchitecture, with no apparent signs of abnormality. Energy Dispersive X-Ray Fluorescence (EDXRF) studies revealed a significant decrease in tissue concentrations of zinc in the colon following DMH treatment, which upon zinc supplementation were recovered to near normal levels. In conclusion, the results of this study suggest that zinc has a beneficial effect during the initiation of key events leading to the development of experimentally induced carcinogenesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Shike M, Winawer SJ, Greenwald PH, Bloch A, Hill MJ, Swaroop SV (1990) Primary prevention of colorectal cancer:the WHO collaborating centre for prevention of colorectal cancer. Bull World Health Org 68:377–385

    PubMed  CAS  Google Scholar 

  2. Pitot HC (1986) Fundamentals of oncology. Marcel Dekker, Inc., New York

    Google Scholar 

  3. Bartsch H, Nair J (2002) Potential role of lipid peroxidation derived DNA damage in human colon carcinogenesis: studies on exocyclic base adducts as stable oxidative stress markers. Cancer Detect Preven 22:308–312

    Article  Google Scholar 

  4. Rogers AE, Nauss KM (1985) Rodent models for carcinoma of the colon. Dig Dis Sci 30:87S-102S

    Article  PubMed  CAS  Google Scholar 

  5. Manju V, Nalini N (2005) Chemopreventive efficacy of ginger, a naturally occurring anticarcinogen during the initiation, post-initiation stages of 1,2 dimethylhydrazine-induced colon cancer. Clin Chim Acta 58:60–67

    Article  CAS  Google Scholar 

  6. Potter JD, McMichael AJ (1986) Diet and cancer of the colon and rectum: a case-control study. J Natl Cancer Inst 76:557–569

    PubMed  CAS  Google Scholar 

  7. Mukhtar H, Athar M (1988) Dietary anticarcinogens and cancer prevention. Clevel Clin J Med 55:507–508

    CAS  Google Scholar 

  8. Carter JW, Lancaster H, Hardman WE, Cameron IL (1997) Zinc deprivation promotes progression of 1,2-dimethylhydrazine-induced colon tumors but reduces malignant invasion in mice. Nutr Cancer 27(3):217–221

    Article  PubMed  CAS  Google Scholar 

  9. Singh KP, Zaidi SIA, Raisuddin S, Saxena AK, Murthy RC, Ray PK (1992) Effect of zinc on immune functions and host resistance against infection and tumor challenge. Immunopharmacol Immunotoxicol 14:813–840

    PubMed  CAS  Google Scholar 

  10. Satoh M, Kondo Y, Mita M, Nakagawa I, Naganuma A, Imura N (1993) Prevention of carcinogenecity of anticancer drugs by metallothionein induction. Cancer Res 53:4767–4768

    PubMed  CAS  Google Scholar 

  11. Soler AP, Miller RD, Laughlin KV, Carp NZ, Klurfeld DM, Mullin JM (1999) Increased tight junctional permeability is associated with the development of colon cancer. Carcinogenesis 20:1425–1431

    Article  PubMed  CAS  Google Scholar 

  12. Goel A, Dani V, Dhawan DK (2005) Protective effects of zinc on lipid peroxidation, antioxidant enzymes and hepatic histoarchitecture in chlorpyrifos-induced toxicity. Chem Biol Interact 156:131–140

    Article  PubMed  CAS  Google Scholar 

  13. Wills ED (1966) Mechanism of lipid peroxide formation in animal tissues. Biochem J 99:667–676

    PubMed  CAS  Google Scholar 

  14. Ellman GL (1959) Tissue sulphydryl groups. Arch Biochem Biophys 82:70–77

    Article  PubMed  CAS  Google Scholar 

  15. Luck H (1971) In: Bergmeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 885–893

  16. Kono Y (1978) Generation of superoxide radical during auto oxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195

    Article  PubMed  CAS  Google Scholar 

  17. Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490

    PubMed  CAS  Google Scholar 

  18. Habig WH, Pabst MJ, Jacoby WB (1974) Glutathione-S-Transferase: the first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    PubMed  CAS  Google Scholar 

  19. Lowry OH, Rorebrough NJ, Farr AL, Randall J (1951) Protein measurement with the folin phenol reagent. J Biol Chem 93:265–275

    Google Scholar 

  20. Dudeja PK, Brasitus TA (1990) 1,2-Dimethylhydrazine-induced alterations in lipid peroxidation in preneoplastic and neoplastic colonic tissues. Biochim Biophys Acta 1046:267–270

    PubMed  CAS  Google Scholar 

  21. Hendrickse CW, Kelly R, Radley S, Donovan IA, Keighley MR, Neoptolemod JP (1994) Lipid peroxidation and prostaglandins in colorectal cancer. Br J Surg 81:1219–1223

    Article  PubMed  CAS  Google Scholar 

  22. Skrzydlewska E, Stanklewicz A, Michalak K, Sulkowaska M, Zalewski B, Piotrowski Z (2001) Antioxidant status and proteolytic-antiproteolytic balance in colorectal cancer. Folia Histochem Cytobiol 39:98–99

    Google Scholar 

  23. Seven A, Civelek S, Inci E, Korkut N, Burçak G (1999) Evaluation of oxidative stress parameters in blood of patients with laryngeal carcinoma. Clin Biochem 32:369–373

    Article  PubMed  CAS  Google Scholar 

  24. Chvapil M, Ryan JN, Zukoski CF (1972) Effect of zinc on lipid peroxidation in liver microsomes and mitochondria. Proc Soc Exp Biol Med 140:642–646

    PubMed  CAS  Google Scholar 

  25. Cabre M, Ferre N, Folch J, Paternain JL, Hernandez M, Castillo D, Joven G, Camps J (1995) Inhibition of hepatic cell nuclear DNA fragmentation by zinc in carbon tetrachloride-treated rats. J Hepatol 31:228–234

    Article  Google Scholar 

  26. Bettger WJ, O’Dell BL (1981) A critical physiological role of zinc in the structure and function of biomembranes. Life Sci 28:1425–1438

    Article  PubMed  CAS  Google Scholar 

  27. Pardeep S, Garg ML, Dhawan DK (2004) Protective role of zinc in nickel induced hepatotoxicity in rats. Chem Biol Interact 15:199–209

    Google Scholar 

  28. Younes M, Siegers CP (1981) Mechanistic aspects of enhanced lipid peroxidation following glutathione dependent depletion in vivo. Chem Biol Interact 34:257–266

    Article  PubMed  CAS  Google Scholar 

  29. Jakoby WB (1978) The glutathione tranferase in detoxification. In: Sies H, Wendel S (Eds) Functions of glutathione in liver and kidney. Springer, Berlin, pp 157–163

    Google Scholar 

  30. Al-Turk WA, Stohs SJ, El-Rashidy FH, Othman S, Shaheen O (1987) Changes in the glutathione, glutathione reductase and glutathione-s-transferase as a function of cell concentration and age. Pharmacology 34:1–8

    Article  PubMed  CAS  Google Scholar 

  31. Ludwig JC, Misiorowski RL, Chvapil M, Seymour MD (1980) Interaction of zinc ions with electron carrying coenzymes NADPH and NADH. Chem Biol Interact 30:25–34

    Article  PubMed  CAS  Google Scholar 

  32. Kyle ME, Miccadie S, Nakae D, Farber JL (1987) Superoxide dismutase and catalase protect cultured hepatocytes from the cytotoxicity of acetaminophen. Biochem Biophys Res Commun 149:889–896

    Article  PubMed  CAS  Google Scholar 

  33. Mates JM, Sanchez-Jimenez F (1999) Antioxidant enzymes and their implications in pathophysiologic processes. Front Biosci 4:334–345

    Article  Google Scholar 

  34. Burton GW, Cheesman KN, Ingold KV, Seater TF (1983) Lipid antioxidants and products of lipid peroxidation as potential tumor protective agents. Biochem Soc Trans 11:261–262

    PubMed  CAS  Google Scholar 

  35. Reddy SB, John Charles M, Naga Raju GJ, Seetharami Reddy B, Seshi Reddy T, Rama Lakshmi PVB, Vijayan V (2004) Trace elemental analysis of cancer-afflicted intestine by PIXE technique. Biological Trace Element Res 102:265–281

    Article  CAS  Google Scholar 

  36. Franklin RB, Feng P, Milon B, Desouki MM, Singh KK, Kajdaksy-Balla A, Bagasra O, Costello LC (2005) hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer. Mol Cancer 4:32

    Article  PubMed  CAS  Google Scholar 

  37. Szmigielski S, Litwin J (1964) The histochemical demonstration of zinc in blood granulocytes-the new test in diagnosis of neoplastic diseases. Cancer 17:1381–1384

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. K. Dhawan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chadha, V.D., Vaiphei, K. & Dhawan, D.K. Zinc mediated normalization of histoarchitecture and antioxidant status offers protection against initiation of experimental carcinogenesis. Mol Cell Biochem 304, 101–108 (2007). https://doi.org/10.1007/s11010-007-9490-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9490-x

Keywords

Navigation