Overexpression of extracellular superoxide dismutase (EC-SOD) in mouse skin plays a protective role in DMBA/TPA-induced tumor formation

Sung Hyun Kim, Myoung Ok Kim, Peng Gao, Cheng A. Youm, Hae Ryoung Park, Sang Ryeul Lee, Kil Soo Kim, Jun Gyo Suh, Hoon Taek Lee, Byung Ju Park, Zae Young Ryoo, Tae Hoon Lee

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Extracellular superoxide dismutase (EC-SOD, EC 1.15.1.1) is a major antioxidant enzyme that is located in the extracellular matrix and on the cell surface. EC-SOD protects against cell and tissue damage initiated by extracellular-produced reactive oxygen species (ROS). We investigated a major role of EC-SOD in the development of tumor formation. In this study, we reported that skin-specific overexpressed EC-SOD transgenic mice showed half the number of tumors compared with the nontransgenic mice in the dimethylbenzanthracene (DMBA)-initiated and a 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted two-stage skin carcinogenesis model. This model showed a significant increase of the epidermal cell proliferation in the nontransgenic mice, but the proliferative response in the transgenic mice was delayed. The 8-hydroxy-2′-deoxyguanosine (8OH-dG) detection assay showed that the oxidative DNA damage was significantly higher in the nontransgenic mice than in the transgenic mice after TPA treatments. Overall, EC-SOD overexpression inhibited the TPA-induced cell proliferation and DNA damage, and reduced the subsequent formation of tumors. Our data suggest that EC-SOD plays a protective role in DMBA/TPA-induced skin carcinogenesis.

Original languageEnglish
Pages (from-to)333-341
Number of pages9
JournalOncology Research
Volume15
Issue number7-8
DOIs
StatePublished - 2005

Keywords

  • 12-O-Tetradecanoylphorbol-13-acetate (TPA)
  • 5-Bromo-2′-deoxy-uridine (BrdU)
  • 8-Hydroxy-2′-deoxyguanosine (8OH-dG)
  • Dimethylbenzanthracene (DMBA)
  • Extracellular superoxide dismutase (EC-SOD)
  • Transgenic mice

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