SKH-1 mouse skin painting: a short-term assay to evaluate the tumorigenic activity of cigarette smoke condensate.
The hairless mouse strain SKH-1 was investigated in a short-term assay to assess the tumorigenic activity of mainstream cigarette smoke condensate (CSC). The design chosen was the two-stage dermal tumorigenicity assay (skin painting), with tumor initiation using a single dermal application of the carcinogen/mutagen dimethylbenz(a)anthracene applied to the back at a non-tumorigenic dose and tumor promotion by repeated dermal applications of CSC at the same site. The mice reproducibly developed skin tumors at the application site after 15 weeks at a frequency that allowed comparison of the treatment groups. The histopathological examination revealed the benign nature of the tumors (keratotic papillomas). Prolongation of the application period to 25 weeks resulted in the development of malignant tumors (carcinomas), indicating that the benign tumors after 15 weeks can be taken as surrogate endpoints for malignancies progressing after further treatment. After 15 weeks, tumor incidence (the percentage of tumor-bearing mice), tumor multiplicity (the number of tumors per mouse), and tumor-onset (the duration of the application period that resulted in a meaningful tumor incidence) were positively correlated with the initiating and promoting dose. The reproducibility of this assay was at least comparable to that described for other skin painting models in the literature. When the assay system was used to compare CSCs to which different concentrations of benzo(a)pyrene were added, its ability to distinguish these different condensate preparations was comparable to that of other models. The results obtained with the SKH-1 mouse strain suggest its usefulness in the short-term skin painting assay for the comparative investigation of the tumorigenic activity of different CSCs.
Philip Morris International R&D, Philip Morris Products SA, Neuchâtel, Switzerland. Ewald.Roemer@pmintl.com
E
E
Roemer
T H
TH
Ottmueller
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HJ
Urban
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C
Baillet-Mignard
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D051379:Mice; D023421:Models, Animal; D044367:Phase Transition; D012867:Skin / Q000187:drug effects*; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
D014028:Tobacco Smoke Pollution; D015127:9,10-Dimethyl-1,2-benzanthracene