© 1991 Oxford University Press
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Constitutively elevated levels of ornithine and polyamines in mouse epidermal papillomas
The Lankenau Medical Research Center Philadelphia, PA 19151
1Department of Biochemical Development and Molecular Diseases,Childrens Hospital of Philadelphia, Philadelphia, PA 19104, USA
Epidermal papillomas were induced in CD-1 mice by a single topical application of 7,12-dimethylbenzanthracene (DMBA)followed by twice weekly applications of 12-0-tetradecanoyl-phorbol-13-acetate W A ) in acetone. Control groups consisted of mice treated singly or chronically with acetone or TPA.TPA induced a rapid, yet transient 500- to 10Wfold increase in ornithine decarboxylase (ODC) activity which resultedin a 2- to 8.4-fold elevation of putrescine in both singly or chronically TPA-treated mouse epidermis 4 - 6 h afterits application. After 24 h, levels of spermidine, but not spermine, were also elevated. The O W and arginase activities in the 11 individual papillomas studied averaged 400- and 26-fold higher respectively than basal levels in epidermis.The activity of ODC in most papillomas, unlike ODC in epidermis, could be stimulated by guanosine 5'-triphosphate (GTP). Putrescine and spermidine levels in papillomas, especially those exhibiting highly GTP-stimulated ODC,were substantially higher compared to either normal or TPA-treated epidermis. Although epidermis contains arelatively high ornithine content, its level is even further elevated in papillomas, in some cases as much as 70-fold.The consequences of the constitutively elevated polyamine levels in papillomas caused by the loss of control over the normally tightly regulated polyamine biosynthetic pathway are not known, but could be important in regulating the balance between proliferation and differentiation in this self renewing epithelial tissue.
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