Control and Mechanism of Tumor Promotion in UV-Carcinogenesis

  • Ueda, Masato (Division of Dermatology, Clinical Molecular Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine) ;
  • Budiyanto, Arief (Division of Dermatology, Clinical Molecular Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine) ;
  • Ashida, Masashi (Division of Dermatology, Clinical Molecular Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine) ;
  • Bito, Toshinori (Division of Dermatology, Clinical Molecular Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine) ;
  • Ichihashi, Masamitsu (Division of Dermatology, Clinical Molecular Medicine, Faculty of Medicine, Kobe University Graduate School of Medicine)
  • Published : 2002.08.01

Abstract

Carcinogenesis can be theoretically divided to intiation step and promotion step. Intiation associates with genetic alterations including p53 tumor suppressor gene and ras oncogene. Promotion involves in clonal expansion of of an initiated cell by epigenetic mechanism, mainly through signal transduction and gene expression. Ultraviolet light (UV) acts as both initiator and promoter. Initiation is closely related with DNA damage induced by UV, including cyclobutane pyrimidine dimers, (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine. Cyclobutane pyrimidine dimers and (6-4) photoproducts are directly induced by UV, while 8-hydroxy-2'-deoxyguanosine is induced indirectly by the reactive oxygen species. Because initiation is an irreversal genetic event, while promotion is a reversal and epigenetic event, to know the molecular mechanisms of tumor promotion in UV-carcinogenesis is crucial to develop preventive medicine and suppress UV-carcinogenesis. Because ROS is also involved in signal transduction of the cell, anti-oxidant could be the good candidate of anti-promoting agent. Here, we describe the suppressive effect of UV-carcinogenesis by various anti-oxidant including olive oil. In addition, we discuss about the mechanism of UVB-induced expression of cyclooxygenase-2, which might be a representative molecule involved in promotion of UV-carcinogenesis.