© 1982 Oxford University Press
research-article |
Effect of retinoic acid pretreatment on 12-O-tetradecanoylphorbol-13-acetate-induced cell population kinetics and polyamine biosynthesis in hairless mouse epidermis
Institute of Pathology, University of Oslo Rikshospitalet, The National Hospital, Oslo 1, Norway
A single topical application of 17 nmol 12-O-tetradecanoyl-phorbol-13-acetate (TPA) to the skin of hairless mice induces characteristic transient alterations in the epidermal cell turnover and maturation (0–96 h), associated in time with characteristic changes in the activities of L-ornithine carboxylyase (E.C. 4.1.1.17 [EC] ) (ODC) and S-adenosyl-L-methionine carboxy-lyase (E.C. 4.1.1.50 [EC] ) (SAM-D) and in the accumulation of polyamines. The effects on these responses of local pretreatment of the skin with retinoic acid 1 h prior to TPA were investigated at selected time points. Retinoic acid inhibited the TPA-induced ODC activity and the ensuing accumulation of putrescine, but did not alter the TPA-induced SAM-D activity or the molar ratio of spermidine/spermine. This pretreatment also decreased the number of dividing basal cells in the first TPA-induced synchronized wave of proliferating cells. However, during the subsequent period of proliferation, the number of dividing cells in the retinoic acid pretreated group was comparatively increased. Hence, at four dose levels of retinoic acid (0.17, 1.70, 17.0 and 170 nmol), which all inhibited the TPA-induced ODC effectively, there was no change in the total number of basal cells that divided during 16–48 h after TPA-application. The theory is put forward that retinoic acid might exert its antitumorigenic effect during tumor promotion with TPA by interfering with the rate and/or quality of epidermal cell maturation, rather than by inhibiting cell proliferation.