Skin tumor development and keratin expression in different experimental models. Relation to inducing agent and target tissue structure.
The applicability of the experimental skin carcinogenesis model for studies of tumor development was examined by exposing the skin of various mouse strains to different chemical carcinogens and UV radiation regimens, in order to analyze the development and progression of the neoplastic process and the role of differentiation markers such as keratins. In tumor-sensitive hairy NMRI mouse skin, the chemical carcinogen, 7,12-dimethylbenz(a)-anthracene (DMBA) induced an abnormal epidermal cell differentiation and structural irregularities associated with an altered keratin expression, as well as numerous papillomas and squamous cell carcinomas. A suboptimal dose of UVB irradiation increased the number of DMBA-induced benign squamous neoplasms. Low doses of benzo(a)pyrene resulted in mild epidermal alterations, but only in one tumor. High doses of UVB induced a large number of undifferentiated spindle cell tumors with few keratinpositive cells in NMRI mice, similar though fewer tumors in hairy, heavily pigmented C57BL/6 mice, numerous papillomas and squamous cell carcinomas in hairless hr/hr mice but only two papillomas in hairy, moderately pigmented DBA/2 mice while UVA exposure produced only two papillomas in hairless SKH-1 mice. In conclusion, the extent and type of skin tumor development depended upon the induction regimen: physical, chemical, dose and duration, as well as on the skin structure: pigmentation and adnexal development, all of which have to be taken into account when relating experimental results to human conditions.
Department of Pathology, University of Oulu, Finland.
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M
Mäkinen
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F
Stenbäck
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002273:Carcinogens; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D004195:Disease Models, Animal; D005260:Female; D007633:Keratins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D012878:Skin Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology
D014408:Biomarkers, Tumor; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D007633:Keratins