Summary
This study examined the effect of nicotine on the expression of mutant p53 (mt-p53) in bladder cancer rats. The rat models of bladder cancer were established by infusing N-methyl-nitroso-urea (MNU, 10 mg/kg every 2 weeks for 8 weeks) into the bladder. Pathological examination on the bladder was conducted to confirm the establishment of the model. All the bladder cancer rats were randomly divided into an MNU group and 3 nicotine groups. In the nicotine groups, the rats were intragastrically administered nicotine at different concentrations (25, 15, 5 mg/kg respectively) 3 times per week for 8 weeks. The mt-p53 expression was detected by the immunohistochemical method. The results showed that rat bladder cancer models developed histopathological changes of bladder transitional cell carcinoma. The positive rate of mt-p53 expression in the 3 nicotine groups (25, 15, 5 mg/kg) was 75.00%, 58.33% and 41.67% by the 14th week, respectively, significantly higher than that in the MNU group (33.33%) (all P<0.05). The mt-p53 expression rate was positively correlated with the medication dose and time (P<0.05). It is concluded that nicotine may play an important role in the development of bladder cancer partially by increasing the expression of mt-p53.
Similar content being viewed by others
References
Wald NJ, Hackshaw AK. Cigarette smoking: an epidemiological overview. Br Med Bull, 1996, 52(1):3–11
Gan J, Skipper PL, Gago Dominguez M, et al. Alkylaniline-hemoglobin adducts and risk of non-smoking-related bladder cancer. J Natl Cancer Inst, 2004,96(19):1425–1431
Qian LX, Liu XL, Ding H, et al. Dynamic observation on histopathological changes in bladder tumor induced by N-methyl-N-nitrosourea in rats. Chin J Exp Surg (Chinese), 2004,21(5):563–564
Chang FH, Liu SZ, Man D, et al. The determination of LD50 of nicotine and empyreumatic oil. Acta Acad Med Nei Mongol (Chinese), 1999, 21(3):190–191
Knowles MA. Tumor suppressor loci in bladder cancer. Front Biosci, 2007,12:2233–2251
Liu YH, Luo CL. Progress in research on p53 gene in bladder cancer. Zhong Guo Gong Ye Yi Xue Za Zhi (Chinese), 2003,16(1):37–40
Mitra AP, Datar RH, Cote RJ. Molecular staging of bladder cancer. BJU Int, 2005, 96(1):7–12
Gomez-Lazaro M, Fernandez-Gomez FJ, Jordan J. p53: twenty-five years understanding the mechanism of genome protection. J Physiol Biochem, 2004, 60(4):287–307
Algaba F, Trias I, Santinelli A, et al. TP53 in urologic tumors. Anal Quant Cytol Histol, 2003,25(3):123–130
Yang CG, Zhang LJ, Li M, et al. Clinical significance of expression of p53 protein and apoptosis in bladder cancer. Practical J Cancer, 2007,22(1):34–36
Syrigos KN, Karapanagiotou E, Harrington KJ. The clinical significance of molecular markers to bladder cancer. Hybrid Hybridomics, 2004,23(6):335–342
Moonen PM, van Balken Ory B, Kiemeney LA, et al. Prognostic value of p53 for high risk superficial bladder cancer with long-term followup. J Urol, 2007,177(1): 80–83
Smith ND, Rubenstein JN, Eggener SE, et al. The p53 tumor suppressor gene and nuclear protein: basic science review and relevance in the management of bladder cancer. J Urol, 2003,169(4):1219–1228
LaRue H, Allard P, Simoneau M, et al. P53 point mutations in initial superficial bladder cancer occur only in tumors from current or recent cigarette smokers. Carcinogenesis, 2000,21(1):101–106
Kelsey KT, Hirao T, Hirao S, et al. TP53 alterations and patterns of carcinogen exposure in a U. S. population-based study of bladder cancer. Int J Cancer, 2005,117(3):370–375
Jemal A, Cokkinides VE, Shafey O, et al. Lung cancer trends in young adults: an early indicator of progress in tobacco control (United States). Cancer Causes Control, 2003,14(6):579–585
Tsurutani J, Castillo SS, Brognard J, et al. Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells. Carcinogenesis, 2005,26(7):1182–1195
Kirk GD, Merlo C, O’Driscoll P, et al. HIV infection is associated with an increased risk for lung cancer, independent of smoking. Clin Infect Dis, 2007, 45(1):103–110
Murta-Nascimento C, Schmitz-Dräger BJ, Zeegers MP, et al. Epidemiology of urinary bladder cancer: from tumor development to patient’s death. World J Urol, 2007,25(3):285–295
Bjerregaard BK, Raaschou-Nielsen O, Sorensen M, et al. Tobacco smoke and bladder cancer-in the European prospective investigation into cancer and nutrition. Int J Cancer, 2006,119(10):2412–2416
Pitard A, Brennan P, Clavel J, et al. Cigar, pipe, and cigarette smoking and bladder cancer risk in European men. Cancer Causes Control, 2001,12(6):551–556
Samanic C, Kogevinas M, Dosemeci M, et al. Smoking and bladder cancer in Spain: effects of tobacco type, timing, environmental tobacco smoke, and gender. Cancer Epidemiol Biomarkers Prev, 2006,15(7):1348–1354
Van Hemelrijck MJ, Michaud DS, Connolly GN, et al. Tobacco use and bladder cancer patterns in three western European countries. J Public Health (Oxf), 2009,31(3): 335–344
Fondrevelle ME, Kantelip B, Reiter RE, et al. The expression of Twist has an impact on survival in human bladder cancer and is influenced by the smoking status. Urol Oncol, 2009,27(3):268–276
Shin VY, Wu WK, Ye YN, et al. Nicotine promotes gastric tumor growth and neovascularization by activating extracellular signal-regulated kinase and cyclooxygenase-2. Carcinogenesis, 2004, 25(12): 2487–2495
Chen RJ, Ho YS, Guo HR, et al. Rapid activation of Stat3 and ERK1/2 by nicotine modulates cell proliferation in human bladder cancer cells. Toxicol Sci, 2008,104(2): 283–293
Puliyappadamba VT, Cheriyan VT, Thulasidasan AK, et al. Nicotine-induced survival signaling in lung cancer cells is dependent on their p53 status while its down-regulation by curcumin is independent. Mol Cancer, 2010,9:220
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Liu, D., Pan, F., Li, B. et al. Intervention of nicotine on MNU-induced bladder cancer in rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 103–106 (2011). https://doi.org/10.1007/s11596-011-0159-z
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-011-0159-z