ON BIOCHEMICAL MECHANISM OF TUMORIGENESIS IN MOUSE SKIN .2. EARLY EFFECTS ON BIOSYNTHESIS OF NUCLEIC ACIDS INDUCED BY INITIATING DOSES OF DMBA AND BY PROMOTING DOSES OF PHORBOL-12.13-DIESTER TPA

A standardized experimental procedure is described for the biochemical determination of the time course and extent of DNA and RNA synthesis in normal and initiated or/and promoted mouse skin. For initiation, a dose of i=10 μmoles of DMBA is administred intragastrically. For promotion, sequential topical applications of 0.06 μmoles of the phorbol-12,13-diester TPA (Croton oil factor A1) are used. Up to one hundred and eighty six hours after pretreatment and after a 40 minute pulse of 3H-thymidine or 3H-uridine the specific activity of the nucleic acids in skin is determined. During the first 24 hours after DMBA a pronounced inhibition of both DNA and RNA synthesis is observed, followed by an intense stimulation. The maximum of the inhibition of RNA synthesis is reached earlier than that of DNA synthesis. Their maxima of stimulation are reached approximately at the same time (48 hours) after pretreatment. Following TPA pretreatment the stimulation of the synthesis of both nucleic acids is practically not preceded by an inhibition. The maximum of stimulation is reached earlier in RNA synthesis than in DNA synthesis. After applying DMBA and TPA simultaneously the inhibition phase as seen after DMBA alone disappeared. The results are discussed with reference to relevant literature and to the biochemical events during initiation and promotion. Various parameters of the experimental procedure are investigated critically. © 1969 Springer-Verlag.