Abstract
Oxidative damage has been suggested to play a role in the pathogenesis of basal cell carcinoma (BCC). This study illustrated an involvement of oxidative DNA damage and changes in antioxidant defenses in BCC by conducting a case-control study (24 controls and 24 BCC patients) and assessing urinary 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dGuo), plasma antioxidant defenses including catalase (CAT), glutathione peroxidase (GPx), NQO1, and total superoxide dismutase (SOD) activities, and glutathione (GSH) levels before surgery and 1 month after surgery. 8-oxo-dGuo expressions as well as protein and mRNA expressions of DNA repair enzyme hOGG1 and antioxidant defenses (CAT, GCLC, GPx, Nrf2, and MnSOD) in nonneoplastic epidermis of control and BCC tissues were also determined. This study observed induction in urinary 8-oxo-dGuo, increased 8-oxo-dGuo expression, and reduced hOGG1 protein and mRNA in BCC tissues, decreased activities of CAT, GPx, and NQO1, but elevated SOD activities and GSH levels in BCC patients and reduction of all antioxidant proteins and genes studied in BCC tissues. Furthermore, decreased plasma antioxidant activities in BCC patients were restored at 1 month after operation compared with preoperative levels. Herein, we concluded that BCC patients were associated with oxidative DNA damage and depletion of antioxidant defenses and surgical removal of BCC correlated with improved redox status.
Highlights
Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer (NMSC) worldwide, in particular, in fair-skinned population and its incidence has been rising over the past several years [1,2,3]
Urinary 8-oxodGuo levels of BCC patients were insignificantly altered at 1 month, they were substantially reduced at 6 months compared to preoperative levels (Figure 1(a))
While preoperative values of plasma CAT, glutathione peroxidase (GPx), and NAD(P)H: quinone oxidoreductase 1 (NQO1) activities were observed to be lower in BCC patients compared to control (Figures 1(b)–1(d)), plasma total superoxide dismutase (SOD) activities and GSH levels were substantially higher in BCC patients compared to control (Figures 1(e)-1(f))
Summary
Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer (NMSC) worldwide, in particular, in fair-skinned population and its incidence has been rising over the past several years [1,2,3]. Excessive reactive oxygen species (ROS) generated by UVR have been shown to contribute to malignant transformation of keratinocytes into cancerous cells including BCC probably through oxidative DNA damage, defects in DNA repair, and interference with cellular signaling [6, 7]. The oxidative modification of guanine leads to formation of 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxo-dGuo), which
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