title: Skin tumours induced by narrowband UVB have higher frequency of p53 mutations than tumours induced by broadband UVB independent of Ogg1 genotype.
abstract: Different wavelengths of ultraviolet (UV) light have different promoting effects on skin carcinogenesis. Narrowband UVB (NB-UVB) has a single-peak wavelength of 311 nm and is widely used for treating skin diseases. Our previous work showed that, in comparison with conventional broadband UVB (BB-UVB), long-term exposure to NB-UVB induces higher frequency of skin cancer in mice, and it suggested that this is mediated through the formation of cyclobutane pyrimidine dimers (CPDs). To explore whether the frequency of p53 mutations in skin tumours correlates with CPD-induced mutations, we compared the frequency and types of p53 mutations between NB-UVB-induced and BB-UVB-induced malignant skin tumours produced in wild-type and Ogg1 knockout mice, which are deficient in repair of oxidative 8-oxoguanine (8-oxoG), a DNA damage mediated by reactive oxygen species (ROS). The frequency of p53 mutation was significantly higher in NB-UVB-induced than in BB-UVB-induced tumours in both wild-type and Ogg1 knockout mice. Most of the p53 mutations found were G:C → A:T transitions at dipyrimidine sites in both the NB-UVB- and BB-UVB-exposed groups. However, G:C → T:A mutations caused by 8-oxoG did not increase in Ogg1 knockout mice exposed to either NB-UVB or BB-UVB. Our results strongly suggest that NB-UVB induces highly malignant tumours caused by p53 dipyrimidine mutations through the formation of CPDs.
authors: Division of Dermatology, Department of Internal Related, Graduate School of Medicine, Kobe University, Kobe, Japan.
authors: Flandiana
authors: F
authors: Yogianti
authors: Makoto
authors: M
authors: Kunisada
authors: Ryusuke
authors: R
authors: Ono
authors: Kunihiko
authors: K
authors: Sakumi
authors: Yusaku
authors: Y
authors: Nakabeppu
authors: Chikako
authors: C
authors: Nishigori
mesh_terms: D000818:Animals; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D016159:Tumor Suppressor Protein p53; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse