Ribosomal RNA Synthesis and Growth in Mouse Epidermis Following Initiation with Dimethylbenzanthracene and Promotion with 12-0-Tetradecanoyl-phorbol-13-acetate

Abstract

The application of 17 nmol of 12-0-tetradecanoyl-phorbol-13-acetate (TPA) onto the backs of CD-1 female mice initiated 7 days earlier with 200 nmol of dimethylbenzanthracene (DMBA) results in a massive accumulation of epidermal ribosomes. Ribosome accumulation reaches a peak in about 2-3 days, and then slowly begins to return toward normal levels. However, by day 10, the end of the experimental period, ribosome levels are still above normal. Marked increase in ribosome synthesis, as indicated by increased incorporation of [5-3H]-undine into epidermal ribosomes, indicates that increased ribosome synthesis plays a major role in the ribosome accumulation. Decreased ribosome synthesis occurs concomitantly with the decrease in ribosome levels. Associated with the increased synthesis and accumulation of epidermal ribosomes is a marked epidermal growth, as evidenced by increases in epidermal wet weight, total protein, and DNA. As ribosome levels gradually return to normal, the epidermis undergoes regression and returns toward its normal size, but by day 10, the end of the experimental period, it is still slightly thicker than normal. To determine whether the initiation process itself affects ribosome levels and epidermal growth, both were measured for a 7-day period following the application of 200 nmol of DMBA. DMBA results in a small but significant accumulation of epidermal ribosomes within 3 hr, which remains elevated throughout the rest of the experimental period. Increased ribosome synthesis, as evidenced by increased incorporation of [5-3H]-uridine into epidermal ribosomes occurs only at 3 hr after DMBA treatment. Associated with the modest accumulation of ribosomes is a small amount of epidermal growth as indicated by small increases in epidermal wet weight and total pretein, but not total DNA. However, small but significant increases in the total number of epidermal nuclei/mm of interfollicular epidermis occur, and there is a significant small increase in mitotic activity at 5 hr after DMBA treatment. We conclude that the application of an initiating dose of DMBA does have some modest effects on ribosome levels and epidermal growth. Some of these effects may persist for the entire 7-day period prior to the first application of TPA. It is our hypothesis that these small changes probably do not significantly affect the massive epidermal growth and ribosome accumulation following the first application of TPA.