Modulation of novel DNA adducts during human uterine cervix cancer progression

  • Authors:
    • Srivani Ravoori
    • Manicka V. Vadhanam
    • Diane D. Davey
    • Cidambi Srinivasan
    • Bala Nagarajan
    • Ramesh C. Gupta
  • View Affiliations

  • Published online on: December 1, 2006     https://doi.org/10.3892/ijo.29.6.1437
  • Pages: 1437-1443
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Abstract

Progressive accumulation of DNA lesions leads to genetic mutations that are central to the process of tumorigenesis. Human cervix provides an ideal system to determine progressive accumulation of DNA adducts in the target tissue because of its accessibility during routine diagnostic checkups. Uterine cervix samples from various pathologies, i.e. normal (n=13), inflammation (n=9), dysplasia (n=5) and different stages of invasive cancer (n=47), were analyzed for DNA adduct burden by modified 32P-postlabeling/TLC systems. Six subgroups of adducts were detected in the following descending order of polarities: P-1, P-2, PL-1, PL-2, L-1 and L-2 (P, polar; L, lipophilic; PL, between polar and lipophilic). No qualitative differences were observed in adduct profiles in the various cervix pathologies analyzed. However, significant quantitative differences were found. Previously known lipophilic adducts increased significantly from normal to cancer (144±61 to 503±51 adducts/109 nucleotides). Interestingly, the newly discovered polar adducts were present at 61- to 527-fold higher levels than lipophilic adducts. Of all the polar adducts, the known mutagenic lesion, 8-oxodeoxyguanosine, predominated in all cervix conditions. Notably, this lesion was elevated 27-fold in inflammation compared with normal cervix (51,058±9,863 versus 1,886±507 adducts/109 nucleotides). The P-1, PL-1, PL-2 and L-1 adducts were elevated 3- to 13-fold in inflammation compared with normal cervix, and were also higher in dysplasia and cancer. Our data suggest that inflammation may be involved in directing the course of disease progression by accumulating higher levels of DNA lesions. The data further suggest the biomarker potential of the newly detected array of DNA adducts.

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December 2006
Volume 29 Issue 6

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

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Spandidos Publications style
Ravoori S, Vadhanam MV, Davey DD, Srinivasan C, Nagarajan B and Gupta RC: Modulation of novel DNA adducts during human uterine cervix cancer progression. Int J Oncol 29: 1437-1443, 2006
APA
Ravoori, S., Vadhanam, M.V., Davey, D.D., Srinivasan, C., Nagarajan, B., & Gupta, R.C. (2006). Modulation of novel DNA adducts during human uterine cervix cancer progression. International Journal of Oncology, 29, 1437-1443. https://doi.org/10.3892/ijo.29.6.1437
MLA
Ravoori, S., Vadhanam, M. V., Davey, D. D., Srinivasan, C., Nagarajan, B., Gupta, R. C."Modulation of novel DNA adducts during human uterine cervix cancer progression". International Journal of Oncology 29.6 (2006): 1437-1443.
Chicago
Ravoori, S., Vadhanam, M. V., Davey, D. D., Srinivasan, C., Nagarajan, B., Gupta, R. C."Modulation of novel DNA adducts during human uterine cervix cancer progression". International Journal of Oncology 29, no. 6 (2006): 1437-1443. https://doi.org/10.3892/ijo.29.6.1437