Oral Nicotine Induces Oxidative Stress and Inflammation but Does Not Subvert Tumor Suppressor and DNA Repair Responses i
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ORIGINAL RESEARCH ARTICLE
Oral Nicotine Induces Oxidative Stress and Inflammation but Does Not Subvert Tumor Suppressor and DNA Repair Responses in Mice Angom Ranjana Devi1 • Mahuya Sengupta1 • Dipu Mani Barman1 Yashmin Choudhury1
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Received: 30 January 2020 / Accepted: 8 June 2020 Ó Association of Clinical Biochemists of India 2020
Abstract Nicotine, responsible for the addictive properties of tobacco, is widely used in nicotine replacement therapy for tobacco use cessation. We investigated the time-dependent effect of treatment with nicotine on the tumor suppressor, DNA repair and immune responses. Swiss Albino mice (laca strain) of both sexes received nicotine dissolved at a dose of 100 lg/ml in 2% sucrose for 24 weeks, by oral gavage, while age- and gender-matched controls received only 2% sucrose for the same period. Nicotine-treated and control mice were sacrificed 6, 16 and 24 weeks post-treatment, and their tissues evaluated for alterations in histology, oxidative stress, TNF-a levels, nitric oxide (NO) and myeloperoxidase (MPO) release, tumor suppressor response and DNA repair response. Statistical significance of results was determined using Students’ t test. The tissues of nicotine treated mice exhibited a large number of multinucleated and binucleated cells, enlarged nuclei and non-uniform distribution of cells, significant increase in expression of TNF-a gene and serum TNF-a, and time-dependent significant increase in lipid peroxidation, protein carbonylation, NO and MPO release when compared to age-and gender-matched controls. The mRNA expression of the tumor suppressor gene p53, its primary regulator Mdm2, and the DNA repair genes Brca2 and Ape1 were significantly elevated, but the
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12291-020-00903-8) contains supplementary material, which is available to authorized users. & Yashmin Choudhury [email protected]; [email protected] 1
Department of Biotechnology, Assam University, Silchar 788011, India
corresponding protein levels remained largely unaltered. In conclusion, treatment with nicotine caused oxidative stress and inflammation which can cause widespread cellular damage from the very onset of treatment, without subverting the tumor suppressor and DNA repair responses. Keywords DNA repair Inflammation Nicotine Oxidative stress Tumor suppressor response
Introduction Cigarette smoking, use of smokeless tobacco, or dual use, is a leading cause of death globally [1]. The addictive potential of tobacco is attributed to its alkaloid, nicotine, which stimulates the nicotinic cholinergic receptors leading to the release of a variety of neurotransmitters including dopamine in the brain. Dopamine signals a pleasurable experience and is critical for the reinforcing effects that promote the self-administration of nicotine [2]. The ill-effects of cigarette smoking [3] and smokeless tobacco use are well established [4]. In an effort to reduce tobacco harm, nicotine replacement therap
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