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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.241 5-Year IF: 1.349 SJR: 0.519 SNIP: 0.613 CiteScore™: 1.61

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v28.i4.90
pages 351-359

Role of Zinc in Modulating Histoarchitectural and Biochemical Alterations During Dimethylhydrazine (DMH)-Induced Rat Colon Carcinogenesis

Anshoo Malhotra
Department of Biophysics, Post Graduate Institute of Medical Education and Research, Chandigarh, India 160047
Vijayta Dani Chadha
Centre for Nuclear Medicine, Institute for Emerging Ares in Science and Technology, and Department of Biophysics, Panjab University, Chandigarh, India
Praveen Nair
Department of Biophysics, Panjab University, Chandigarh, India
Devinder K. Dhawan
Department of Biophysics and Centre of Nuclear Medicine, Institute for Emerging Areas in Science and Technology, Panjab University, Chandigarh, India

ABSTRACT

The aim of the present work was to gain insight into the putative anticancer effect of dietary zinc during 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis. The rats were segregated into four groups, namely, normal control, DMH-treated, zinc-treated, and (DMH + zinc)-treated. Colon carcinogenesis was induced through weekly subcutaneous injections of DMH (30 mg/kg body weight) for 12 weeks. Zinc in the form of zinc sulfate was supplemented to rats at a dose level of 227 mg/L in drinking water, ad libitum for the entire duration of the study. The effects of different treatments were studied on lipid peroxidation (LPO), reduced glutathione (GSH), and anitioxidative enzymes, which included superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), glutathione reductase (GR), as well as on the histoarchitecture of the colon. A total of 12 weeks of DMH treatment resulted in a significant increase in LPO. GSH levels and the activities of SOD, CAT, and GST were found to be significantly decreased following DMH treatment. A significant elevation in the activity of GR was observed following 12 weeks of DMH treatment. Histopathological studies showed well-differentiated signs of dysplasia, which included nuclei enlargement, epithelial thickening, and nuclear pleomorphism indicative of promotional phase of colon carcinogenesis in DMH-administered rats. Administration of zinc to DMH-treated rats decreased the levels of LPO and GSH significantly, but the activities of SOD and CAT were found to be significantly increased following zinc treatment. Zinc supplementation along with DMH treatment did not reveal any significant change in the activity of GR but significantly improved the activity of GST, which was depressed following DMH treatment. Also, zinc treatment in DMH-treated rats showed signs of great improvement, but structureless masses of the cells and hyperchromic nuclei were still visible occasionally. In conclusion, the results of this study suggest that zinc has a positive beneficial effect against chemically DMH-induced colonic preneoplastic progression in rats.


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