Effects of 12-O-tetradecanoylphorbol-13-acetate on the incorporation of labelled precursors into RNA, DNA and protein in epidermis, dermis and subcutis from precancerous mouse skin with reference to enhanced tumorigenesis

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Abstract
The effects of a single application of 1.8 nmol 12-0-tetradecanoylphorbol-13-acetate (TPA) on precursor incorporation into RNA, DNA and protein in the epidermis, dermis and subcutis from 3-methylcholanthrene (MCA) injected precancerous mouse skin were studied at various time points between 3-96 h. In the precancerous tissues, the rates of incorporation of [3H]uridine into RNA did not alter appreciably from those in the control tissues; while the rates of [3H]methylthymidine incorporation into DNA were elevated with peaks appearing between 6-12 h, at 24 h and at 72 h in epidermis, dermis and subcutis. The rate of incorporation of [14C]leucine into protein was markedly elevated in all the three tissues which showed 3-4 sharp peaks. The maximum stimulation ranged between 14-20 times that of the control. A single application of TPA to the precancerous mouse skin induced early stimulation of precursor incorporation into all the 3 macromolecules in epidermis, dermis and subcutis. The increased stimulation was maintained for 36-72 h. The patterns of incorporation of [3H]methylthymidine into DNA gave rise to 2-3 peaks of elevated uptake in each tissue up to 36-48 h. A lowered rate of DNA synthesis between 48-60 h was followed by a peak at 72 h. In each group, epidermal mitotic activity correlated well with spurts of precursor incorporation into cellular DNA. The observations indicate that TPA recruits more cells into the DNA synthetic phase and accelerates selective growth of preneoplastic cells during tumor progression.