PMID- 1909938 OWN - NLM STAT- MEDLINE DCOM- 19911023 LR - 20190510 IS - 0143-3334 (Print) IS - 0143-3334 (Linking) VI - 12 IP - 9 DP - 1991 Sep TI - Constitutively elevated levels of ornithine and polyamines in mouse epidermal papillomas. PG - 1619-25 AB - 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-O-tetradecanoyl-phorbol-13-acetate (TPA) in acetone. Control groups consisted of mice treated singly or chronically with acetone or TPA. TPA induced a rapid, yet transient 500- to 1000-fold increase in ornithine decarboxylase (ODC) activity which resulted in a 2- to 8.4-fold elevation of putrescine in both singly or chronically TPA-treated mouse epidermis 4-6 h after its application. After 24 h, levels of spermidine, but not spermine, were also elevated. The ODC 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 a relatively 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. FAU - Koza, R A AU - Koza RA AD - Lankenau Medical Research Center, Philadelphia, PA 19151. FAU - Megosh, L C AU - Megosh LC FAU - Palmieri, M AU - Palmieri M FAU - O'Brien, T G AU - O'Brien TG LA - eng GR - ES-01664/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Carcinogenesis JT - Carcinogenesis JID - 8008055 RN - 0 (Polyamines) RN - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene) RN - 86-01-1 (Guanosine Triphosphate) RN - E524N2IXA3 (Ornithine) RN - EC 4.1.1.17 (Ornithine Decarboxylase) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - 9,10-Dimethyl-1,2-benzanthracene/toxicity MH - Animals MH - Female MH - Guanosine Triphosphate/metabolism MH - Mice MH - Mice, Inbred Strains MH - Ornithine/*analysis MH - Ornithine Decarboxylase/metabolism MH - Papilloma/chemically induced/*chemistry MH - Polyamines/*analysis MH - Skin Neoplasms/chemically induced/*chemistry MH - Tetradecanoylphorbol Acetate/toxicity EDAT- 1991/09/01 00:00 MHDA- 1991/09/01 00:01 CRDT- 1991/09/01 00:00 PHST- 1991/09/01 00:00 [pubmed] PHST- 1991/09/01 00:01 [medline] PHST- 1991/09/01 00:00 [entrez] AID - 10.1093/carcin/12.9.1619 [doi] PST - ppublish SO - Carcinogenesis. 1991 Sep;12(9):1619-25. doi: 10.1093/carcin/12.9.1619.