Correlation of the Inhibition by Retinoids of Tumor Promoter-induced Mouse Epidermal Ornithine Decarboxylase Activity and of Skin Tumor Promotion

摘要: Application of the potent tumor promoter, 12- O -tetradecanoylphorbol-13-acetate (TPA), to mouse skin leads a more than 200-fold increase in epidermal ornithine decarboxylase (EC 4.1.1.17) activity, phenotypic change proposed be essential for promotion. The correlation between TPA-induced activity and promotion received additional support from our finding that vitamin A acid its analogs inhibit both formation papillomas. The induction was investigated following multiple applications TPA initiated with dimethylbenz[a]anthracene, regimen followed initiation-promotion experiments. Ornithine increased about 600-fold during repeated 17 nmol TPA. 1.7 retinoic 1 hr prior each treatment inhibited by 60 80%. In experiments, application or before reduced 57 75%, respectively, number papillomas per mouse. contrast, 24 after did not suppress papillomas. Furthermore, at various times relative time initiation dimethylbenz[a]anthracene alter development tumors. The trimethylmethoxyphenyl analog ethyl retinoate, 13- cis -retinoic acid, dimethylmethoxyethylcyclopentenyl as well trimethylhydroxyphenyl retinoate 13-trifluoromethyltrimethylmethoxyphenyl altered neither nor Treatment retinoids result any sign local toxicity; also, average weight control mice identical those treated retinoids. retinoid specifically resultant increases putrescine levels, but it S -adenosyl-l-methionine 4.1.1.50) accumulation spermidine spermine. The results indicate possible mechanism prevention involves their ability associated elevated levels. These findings suggest assay inhibition may simple, rapid screen antipromoting properties new synthetic