Dose- and time-dependent expression of transforming growth factor-β1 mRNA and protein in mouse epidermis and papillomas after repeated topical application of benzo[a]pyrene
| Autor: | Marian L. Miller, James H. Sherman, Roy E. Albert, C. Stuart Baxter |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Cancer Research
medicine.medical_specialty Skin Neoplasms Time Factors Ratón Administration Topical Gene Expression Biology Mice chemistry.chemical_compound Transforming Growth Factor beta Skin Physiological Phenomena Internal medicine Gene expression Benzo(a)pyrene medicine Animals RNA Messenger Molecular Biology Carcinogen Skin Mice Inbred ICR Messenger RNA Dose-Response Relationship Drug Papilloma Epidermis (botany) Immunohistochemistry Neoplasm Proteins Endocrinology chemistry Toxicity Female Epidermis Transforming growth factor |
| Zdroj: | Molecular Carcinogenesis. 8:264-271 |
| ISSN: | 1098-2744 0899-1987 |
| Popis: | Topical weekly application of 64 micrograms of benzo[a]pyrene (BAP) for 4 wk induced transforming growth factor (TGF)-beta 1 mRNA in the epidermis of Swiss (ICR) mice, with a maximum at 6-12 h after the last treatment. The increase in TGF-beta 1 mRNA concentration was accompanied by an increase in immunohistochemically detectable intracellularly localized TGF-beta 1 protein in the suprabasal epidermis and by the appearance of extracellularly localized TGF-beta 1 in the basal layers. A dose rate of 16 micrograms/wk for 4 wk was unable to induce the same response. In contrast, after 20 weekly topical applications of 16 or 64 micrograms of BAP, an increase in TGF-beta 1 mRNA concentration and the appearance of extracellularly localized protein in the epidermis were observed. These changes in TGF-beta 1 expression were paralleled by changes in epidermal morphology. A similar group of animals treated with 4 micrograms of BAP/wk for 20 wk did not respond differently from untreated controls. Papillomas resulting from treatment with 16 or 64 micrograms of BAP/wk for 28 wk stained for intracellularly localized TGF-beta 1 predominantly in the differentiating and nondividing layers. Papillomas stained for extracellularly localized TGF-beta 1 solely in the less differentiated and dividing cells. These results suggest that tumorigenesis by BAP involves the induction of cumulative changes in epidermal TGF-beta 1 mRNA and protein concentrations as well as alterations in skin morphology associated with a tumor-promotion process. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text