Devi Angom Ranjana, Sengupta Mahuya, Barman Dipu Mani, Choudhury Yashmin
Department of Biotechnology, Assam University, Silchar, 788011 India.
Indian J Clin Biochem. 2021 Jul;36(3):296-303. doi: 10.1007/s12291-020-00903-8. Epub 2020 Jun 13.
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 µg/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-α levels, nitric oxide (NO) and myeloperoxidase (MPO) release, tumor suppressor response and DNA repair response. Statistical significance of results was determined using Students' 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 - gene and serum TNF-α, 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 , its primary regulator , and the DNA repair genes and were significantly elevated, but the 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.
尼古丁是烟草具有成瘾性的原因，广泛用于戒烟的尼古丁替代疗法。我们研究了尼古丁治疗对肿瘤抑制、DNA修复和免疫反应的时间依赖性影响。通过口服灌胃法，将100μg/ml尼古丁溶解于2%蔗糖溶液中，对雌雄瑞士白化小鼠（laca品系）进行为期24周的给药，而年龄和性别匹配的对照组在同一时期仅给予2%蔗糖溶液。在治疗后6周、16周和24周处死尼古丁处理组和对照组小鼠，并对其组织进行组织学、氧化应激、TNF-α水平、一氧化氮（NO）和髓过氧化物酶（MPO）释放、肿瘤抑制反应和DNA修复反应的改变评估。结果的统计学显著性采用学生t检验确定。与年龄和性别匹配的对照组相比，尼古丁处理组小鼠的组织出现大量多核和双核细胞、细胞核增大以及细胞分布不均，-基因和血清TNF-α表达显著增加，脂质过氧化、蛋白质羰基化、NO和MPO释放随时间显著增加。肿瘤抑制基因、其主要调节因子以及DNA修复基因和的mRNA表达显著升高，但相应的蛋白质水平基本未改变。总之，尼古丁治疗会引起氧化应激和炎症，从治疗开始就会导致广泛的细胞损伤，而不会破坏肿瘤抑制和DNA修复反应。
