Overexpression of extracellular superoxide dismutase (EC-SOD) in mouse skin plays a protective role in DMBA/TPA-induced tumor formation.
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.
Kim
Sung-Hyun
SH
School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
Kim
Myoung-Ok
MO
Gao
Peng
P
Youm
Cheng A
CA
Park
Hae-ryoung
HR
Lee
T Sang-ryeul
TS
Kim
Kil-Soo
KS
Suh
Jun-Gyo
JG
Lee
Hoon-taek
HT
Park
Byung-Ju
BJ
Ryoo
Zae-Young
ZY
Lee
Tae-Hoon
TH
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D002273:Carcinogens; D049109:Cell Proliferation; D004249:DNA Damage; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017382:Reactive Oxygen Species / Q000009:adverse effects; D012867:Skin / Q000201:enzymology / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate
D002273:Carcinogens; D017382:Reactive Oxygen Species; D015127:9,10-Dimethyl-1,2-benzanthracene; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D013755:Tetradecanoylphorbol Acetate