Cigarette smoke condensate-induced oxidative DNA damage and its removal in human cervical cancer cells

  • Authors:
    • Afsoon Moktar
    • Rajesh Singh
    • Manicka V. Vadhanam
    • Srivani Ravoori
    • James W. Lillard
    • C. Gary Gairola
    • Ramesh C. Gupta
  • View Affiliations

  • Published online on: Wednesday, June 29, 2011
  • Pages: 941-947
  • DOI: 10.3892/ijo.2011.1106

Abstract

Exposure to cigarette smoke is well documented to increase oxidative stress and could account for higher risk of cervical cancer in smokers. Cervical pre-cancerous lesions that are initiated by human papillomavirus (HPV) infection generally regress in the absence of known risk factors such as smoking. 8-oxodeoxyguanosine (8-oxodG) is a highly mutagenic oxidative DNA lesion that is formed by the oxidation of deoxyguanosine. In the present study, we examined: a) the effect of cigarette smoke condensate (CSC) on 8-oxodG formation in and its removal from HPV-transfected (ECT1/E6 E7), HPV-positive (CaSki) and HPV-negative (C33A) human cervical cancer cells, and b) the cell cycle progression and apoptosis in CSC-treated ECT1/E6 E7 cells. CSC induced 8-oxodG in a dose- (p=0.03) and time (p=0.002)-dependent fashion in ECT1/E6 E7 cells as determined by flow cytometry. A 2.4-fold higher level of 8-oxodG was observed in HPV-positive compared with HPV-negative cells. However, 8-oxodG lesions were almost completely removed 72 h post-exposure in all cell lines as determined by ImageStream analysis. This observation correlates with the 2- and 5-fold increase in the p53 levels in ECT1/E6 E7 and CaSki cells with no significant change in C33A cells. We conclude that: a) cigarette smoke constituents induce oxidative stress with higher burden in HPV-positive cervical cancer cells and b) the significant increase observed in p53 levels in wild-type cervical cells (ECT1/E6 E7 and CaSki) may be attributed to the p53-dependent DNA repair pathway while a p53-independent pathway in C33A cells cannot be ruled out.
Journal Cover

October 2011
Volume 39 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Moktar, A., Singh, R., Vadhanam, M., Ravoori, S., Lillard, J., Gairola, C., & Gupta, R. (2011). Cigarette smoke condensate-induced oxidative DNA damage and its removal in human cervical cancer cells. International Journal of Oncology, 39(4), 941-947.
MLA
Moktar, Singh, Vadhanam, Ravoori, Lillard, Gairola, and Ramesh Gupta. "Cigarette smoke condensate-induced oxidative DNA damage and its removal in human cervical cancer cells." International Journal of Oncology International Journal of Oncology 39.4 (2011): 941-947.
Chicago
Moktar, Singh, Vadhanam, Ravoori, Lillard, Gairola, and Ramesh Gupta. "Cigarette smoke condensate-induced oxidative DNA damage and its removal in human cervical cancer cells." International Journal of Oncology International Journal of Oncology 39 no. 4 (2011): 941-947.