Cellular aspects of photocarcinogenesis.
Many aspects are involved in photocarcinogenesis. Historically, genetic change caused by UV-B-induced pyrimidine photoproducts have been paid much attention. Indeed they are very important factors. However, recent reports indicate the involvement of many other factors. First, UV-B induces not only pyrimidine photoproducts but also DNA lesions modified by reactive oxygen species (ROS). Several reports pointed out that types of mutations that are not theoretically caused by pyrimidine photoproducts are frequently observed in the human skin cancers of sun-exposed areas and UV-B-induced murine skin cancers. In addition to transition-type mutations at dipyrimidine sites, mutations which may be induced by the presence of oxidative DNA damage, are frequently observed in the ras oncogene and p53 tumor suppressor gene in human skin cancers of sun-exposed area and in UV-induced mouse skin cancers. Second, recent studies have shown that not only UV-B but also UV-A is involved in photocarcinogenesis based on animal experiments whereas UV-B has been considered mostly responsible. UV-A induces indirect DNA damage via ROS and lipid peroxidation. ROS have been associated not only with initiation, but promotion and progression in the multistage carcinogenesis model. Third, biological responses other than direct influence by UV such as inflammatory and immunological responses and oxidative modifications of DNA and proteins appears also responsible for carcinogenesis. Persistent oxidative stress in cancer may also cause activation of transcription factors and protooncogenes such as c-fos and c-jun as well as genetic instability. Such a stress may also contribute to maintain their malignant characteristics. An integrated model for photocarcinogenesis is proposed.
Nishigori
Chikako
C
Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe University, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. chikako@med.kobe-u.ac.jp
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000528:radiation effects*; D004247:DNA / Q000235:genetics / Q000276:immunology / Q000528:radiation effects; D006801:Humans; D007249:Inflammation; D051379:Mice; D009154:Mutation / Q000235:genetics; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000276:immunology; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000009:adverse effects; D012867:Skin / Q000166:cytology* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics* / Q000276:immunology; D014466:Ultraviolet Rays / Q000009:adverse effects
D017382:Reactive Oxygen Species; D004247:DNA