Overexpression of Extracellular Superoxide Dismutase (EC-SOD) in Mouse Skin Plays a Protective Role in DMBA/TPA-Induced Tumor Formation

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.

The effects of various antioxidants on the development of parthenogenetic porcine embryos

“…EC-SOD overexpression mouse model have been generated in our previous study (Kim et al 2005). A diagram illustrating the DNA cassette used to generate transgenic mice is shown in Fig.…”

Models of reactive oxygen species in cancer

“…However, the SOD3 −/− mice were vulnerable to stress under a high oxygen condition [33]. In addition, a SOD3 transgenic mouse model (SOD3 TG ) with skin-specific over-expression was generated by fusion of mouse SOD3 cDNA with a keratinocyte-specific promoter [34]. Compared to wild-type mice, oxidative DNA damage was decreased in SOD3 TG mice after topical treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA).…”

Cancer, Oxidative Stress, and Metastasis

“…Mice heterozygous for a null allele of Sod2 also form tumors, particularly lymphoma and pituitary adenoma (Van Remmen et al 2003). Sod3-deficient mice do not form tumors, but SOD3 overexpression reduces tumor formation by 50% in a skin carcinogenesis model (Kim et al 2005). Peroxiredoxin1 (Prdx1)-deficient mice develop lymphomas, sarcomas, and carcinomas (Neumann et al 2003).…”