Topical application of retinoic acid induces murine epidermal proliferation without reducing the cell cycle time. A bivariate BrdUrd/DNA flow cytometric study.

Topical application of retinoic acid (RA) induces skin irritation, increased epidermal DNA synthesis and hyperplasia by an unknown mechanism, possibly in common with other hyperplasiogens. To further characterize this regeneration-like effect of RA, the cell cycle traverse in hairless mouse epidermis in vivo after application of a single dose of 100 nmol RA was investigated. Two BrdUrd labelled basal cell cohorts, one exposed to RA during the S phase, the other stimulated by RA into S phase 16 h earlier, were followed for 30 h in their progression through the cell cycle. The basal cells were isolated and prepared for bivariate BrdUrd/DNA flow cytometry analysis (FCM). Both cohorts showed induced proliferation of cells stimulated from G0/G1 into S phase as shown by increase in the S phase fraction, but without reduction in cell cycle time as expected for regenerative growth. This implies that RA stimulates proliferation differently than other hyperplasiogens, and hence may induce irritation and growth stimulation through another mechanism.