title: Tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in an ultra-short-term skin carcinogenesis bioassay using rasH2 mice.
abstract: Assessment of the skin tumor-promoting potential of 12-O-tetradecanoylphorbol-13-acetate (TPA) after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) was conducted using rasH2 transgenic (Tg) mice and their nontransgenic (non-Tg) littermates. Mice were treated with DMBA (50 μg/100 μL acetone) on clipped back skin at the commencement of the study, and 1 week thereafter, TPA was applied at 8 μg/200 μL or 4 μg/200 μL acetone, once or twice weekly, for 7 weeks. Skin nodules were observed in the rasH2 Tg mice from week 4, and the incidence reached 100% at weeks 5 and 6. The number of skin nodules (multiplicity) in the 8-μg twice-weekly, 8-μg once-weekly, 4-μg twice-weekly, and 4-μg once-weekly groups was 62.4, 46.2, 62.6, and 36.9, respectively. The non-Tg mice also developed skin nodules, but the sensitivity to induction in the rasH2 Tg mice was higher. No nodules were observed in the acetone groups, but single nodules were apparent in the no-treatment rasH2 Tg and non-Tg groups. In conclusion, skin promotion effects could be detected within only 8 weeks in the rasH2 mice, and the concentration of 4 μg TPA once weekly was sufficient as a positive control. This short-term skin carcinogenesis bioassay using rasH2 mice could represent a useful tool for the assessment of drug and chemical safety with cutaneous treatment.
authors.affiliation: DIMS Institute of Medical Science, Inc., 64 Goura, Nishiazai, Azai-cho, Ichinomiya 491-0113, Japan. Email: kawabe@dims.co.jp.
authors.forename: M
authors.initials: M
authors.lastname: Kawabe
authors.forename: K
authors.initials: K
authors.lastname: Urano
authors.forename: M
authors.initials: M
authors.lastname: Suguro
authors.forename: T
authors.initials: T
authors.lastname: Numano
authors.forename: F
authors.initials: F
authors.lastname: Taguchi
authors.forename: H
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: F
authors.initials: F
authors.lastname: Furukawa
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D063646:Carcinogenesis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D015127:9,10-Dimethyl-1,2-benzanthracene; D013755:Tetradecanoylphorbol Acetate
keywords: DMBA; TPA; rasH2 mouse; ultra-short-term skin carcinogenesis bioassay