G2 phase cell cycle arrest in human skin following UV irradiation.
The contribution of the short wavelength ultraviolet (UV) component of sunlight to the aetiology of skin cancer has been widely acknowledged, although its direct contribution to tumour initiation or progression is still poorly understood. The loss of normal cell cycle controls, particularly checkpoint controls, are a common feature of cancer. UV radiation causes both G1 and G2 phase checkpoint arrest in vitro cultured cells. In this study we have investigated the cell cycle responses to suberythemal doses of UV on skin. We have utilized short-term whole organ skin cultures, and multi parameter immunohistochemical and biochemical analysis to demonstrate that basal and suprabasal layer melanocytes and keratinocytes undergo a G2 phase cell cycle arrest for up to 48 h following irradiation. The arrest is associated with increased p16 expression but no apparent p53 involvement. This type of organ culture provides a very useful model system, combining the ease of in vitro manipulation with the ability to perform detailed molecular analysis in a normal tissue environment.
Pavey
S
S
Joint Experimental Oncology Program, Department of Pathology, University of Queensland, Herston Road, Brisbane, Queensland 4006, Australia.
Russell
T
T
Gabrielli
B
B
D001973:Bromodeoxyuridine / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000096:biosynthesis; D002453:Cell Cycle / Q000528:radiation effects*; D002478:Cells, Cultured; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis; D016195:G2 Phase / Q000528:radiation effects*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D009924:Organ Culture Techniques; D019000:Phosphotyrosine / Q000737:chemistry; D011233:Precipitin Tests; D012867:Skin / Q000528:radiation effects*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D014466:Ultraviolet Rays; D015854:Up-Regulation
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016159:Tumor Suppressor Protein p53; D019000:Phosphotyrosine; D016203:CDC2 Protein Kinase; D001973:Bromodeoxyuridine