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 language | English |
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Pages (from-to) | 333-341 |
Number of pages | 9 |
Journal | Oncology Research |
Volume | 15 |
Issue number | 7-8 |
DOIs | |
State | Published - 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