The expression of p53, p21, Bax and induction of apoptosis in normal volunteers in response to different doses of ultraviolet radiation

Background: Ultraviolet radiation (UVR) damages keratinocytes. Direct DNA damage may undergo enzymatic repair followed by resumption of the normal cell cycle. Cells may also be eliminated without inflammation by the error-free process of programmed cell death or apoptosis. Necrosis of cells can occur after overwhelming damage. Failure of apoptosis leads to retention of cells with persistent mutations. Objectives: This study investigates p53-dependent apoptotic responses in normal skin following solar-simulated radiation (SSR). Methods: Sun-protected buttock skin from normal volunteers with no history or clinical evidence of skin cancer was exposed to graded doses of SSR, 0.5, 1, 2 and 3 times the minimal erythema dose (MED). Biopsies taken at a range of time points (4.5, 9, 24, 33, 48 and 72 h) after UVR, quantified the time course and dose-response of apoptosis and the expression of the relevant proteins, p53, p21^waf1/Cip1 and Bax, by single and double labelling techniques. Results: Apoptosis was upregulated in a dose-dependent manner as was the expression of p53, p21^waf1/Cip1 and Bax in response to SSR. Following exposure to 3 MEDs it was found that: (i) the maximum number of apoptotic cells occurred at 48 h; (ii) p53 protein expression was upregulated from 4 to 72 h preceding peak p21^waf1/Cip1 protein expression (9-48 h) and peak Bax protein expression (33 h). Conclusions: These results suggest that, following SSR, normal human skin induces apoptosis by the p53, p21^waf1/Cip1, Bax pathway in vivo. In addition, induction of apoptosis and expression of p53, p21^waf1/Cip1 and Bax occurs in a dose-dependent manner.