Blue light inhibits the growth of skin tumors in the v-Ha-ras transgenic mouse.
12-O-Tetradecanoylphorbol-13-acetate (TPA) was applied to the back skin of v-Ha-ras (TG-AC) female transgenic mice at a dose of 2.5 microg/200 microl twice a week for 9 weeks. The back skin was then exposed to blue light (wavelength, 470 nm; irradiance, 5.7 mW/cm2) for 1 h daily for 9 weeks. The mice to which TPA was applied developed skin tumors at 6 weeks after the start of application. The tumor incidence rates at 6, 7, 8 and 9 weeks after the start of application were 70%, 80%, 100% and 100%, respectively, and the numbers of tumors 1 mm or more in diameter were 1, 5, 10 and 19, respectively. In the mice that were exposed to blue light after TPA application, the tumor incidence rates were 10%, 40%, 60% and 80%, respectively, and the numbers of tumors 1 mm or more in diameter were 0, 2, 5 and 9, respectively. Histopathological examination of the skin revealed that TPA application induced diffuse hyperplasia, exaggerated keratinization, and papillomas in all 10 mice. A localized form of epidermal hyperplasia was also observed in 4 mice. The incidence rate of papillomas in the mice that were exposed to blue light after TPA application was lower and the degree of exaggerated keratinization was greater. Exaggerated keratinization was considered to represent a regressive change following exposure. These findings suggest that exposure to blue light may be a promising new approach in the treatment of skin tumors.
Ohara
Masayuki
M
Otsuka Pharmaceutical Factory Inc., Muya-cho, Naruto, Tokushima 772-8601. oharams@otsukakj.co.jp
Kawashima
Yuzo
Y
Kitajima
Shunichi
S
Mitsuoka
Chihomi
C
Watanabe
Hiromitsu
H
D000818:Animals; D004817:Epidermis / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D005260:Female; D011905:Genes, ras; D006965:Hyperplasia; D007633:Keratins / Q000032:analysis; D051379:Mice; D008822:Mice, Transgenic; D015689:Oncogene Protein p21(ras) / Q000502:physiology; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D010789:Phototherapy; D011230:Precancerous Conditions / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012871:Skin Diseases / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate; D015430:Weight Gain
D011993:Recombinant Fusion Proteins; D007633:Keratins; D015689:Oncogene Protein p21(ras); D013755:Tetradecanoylphorbol Acetate