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Journal of Environmental Pathology, Toxicology and Oncology
Facteur d'impact: 1.625 Facteur d'impact sur 5 ans: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Imprimer: 0731-8898
ISSN En ligne: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2017021847
pages 245-267

Aqueous Extract of Smokeless Tobacco (gutkha) Deregulates Tumor Suppressor and DNA Repair Response in a Murine Model of Smokeless Tobacco Use

Angom Ranjana Devi
Department of Biotechnology, Assam University, Silchar-788011, India
Mahuya Sengupta
Department of Biotechnology, Assam University, Silchar-788011, India
Yashmin Choudhury
Department of Biotechnology, Assam University, Silchar-788011, India

RÉSUMÉ

The effect of smokeless tobacco (gutkha) was investigated by treating male and female Swiss Albino mice with an aqueous extract of smokeless tobacco (AEST). AEST was administered at a dose of 25 mg kg-1 body weight per day for different time periods (6, 12, 16, and 24 weeks), and control animals were provided only drinking water without AEST for the same period. Control and AEST-treated mice were observed for different oxidative stress parameters, nitric oxide (NO) release, and myeloperoxidase (MPO) release, and they were evaluated for alterations in tumor suppressor and DNA repair responses in the liver and spleen. Both male and female mice treated with AEST showed significant increase in lipid peroxidation, protein carbonylation, and NO and MPO release in the liver and spleen compared to age- and gender-matched controls. The significant decline in tumor suppressor p53 protein levels, likely mediated by concomitantly upregulated levels of Mdm2, was observed. We also observed a significant decline in the levels of DNA repair proteins Brca2 and Ape-1 compared to the respective controls. Thus, AEST induces oxidative stress, inflammation, and significantly lowers tumor suppressor and DNA repair responses. These factors may work in conjunction to increase the risk for certain diseases, including cancer.


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