Sodium o-phenylphenate (OPP-Na) promotes skin carcinogenesis in CD-1 female mice initiated with 7, 12-dethylbenz[a]anthracene

Abstract

Sodium o-phenylphenate (OPP-Na) was applied at a dose level of 5.0 mg/animal dermally to the fur-clipped dorsal area of female CD-I mice twice weekly for 47 weeks after applications of 10 μg of 7, 12-dimethylbenz[a]anthracene (DMBA) as an initiator twice weekly for 5 weeks. A total of 25 skin tumors (21 papillomas and four carcinomas) developed in 15 out of 20 mice (75%). The incidence and yield of skin tumors in this DMBA/OPP-Na group were significantly higher than in the DMBA/acetone-treated group where only six tumors (five papillomas and one carcinoma) were observed in five out of 20 mice (25%). Only one papilloma developed in OPP-Na/12-o-tetradecanoylphorbol 13-acetate (TPA) treated animals (initiation testing group), and no tumors were observed in mice receiving OPP-Na/acetone. OPP-Na elevated 5-bromodeoxyuridine(BrdU) incorporation in basal cells of mouse epidermis dose-relatedly and the thickness of the skin in the treated group was also increased to ¨ 2- or 3-fold that of controls. In addition, high dose application (20 mg/mouse) caused ukeration. O-Phenylphenol (OPP) administration was associated with extensive corrosive effects. The data suggest that OPP-Na is an ulcerogenk agent which induces epidermal proliferation and which can act as a promoter, but not as an initiator or a complete carcinogen, in two-stage mouse skin carcinogenesis.