UVB-induced experimental carcinogenesis: dysregulation of apoptosis and p53 signalling pathway

Abstract

UVB irradiation is a major cause of human skin cancer. In addition to inducing neoplastic changes, UVB irradiation also causes immune suppression which may impair local defence reactions allowing abnormal cells to proliferate and develop into skin tumours.¹ The immuno-suppressive events induced by UVB irradiation are mediated by a number of pathways involving altered DNA,² cis-urocanic acid (cis-UCA),³ IL-10,⁴ and mast cells.⁵ UVB-damaged DNA can result in mutations including those of p53, allowing the proliferation of aberrant cells and, ultimately, local tumour invasion. In p53 gene knockout mice, development of skin tumours increases more rapidly after exposure to UVB irradiation.⁶ p53 as a target for UV-induced mutations in developing murine and human skin cancer involves C→T and CC→TT transitions at dipyrimidine sites.⁷ This paper summarises the adaptive responses in mouse skin following acute and chronic UV irradiation.