Proliferation-dependent effect of skin extracts (chalone) on mouse epidermal cell flux at the G1-S, S-G2 and G2-M transitions.

Epidermal cell proliferation in mice was studied from 4 to 11 h following a single intraperitoneal (IP) injection of a crude skin extract. Cell cycle flux parameters were evaluated by a combination of several methods. The G1-S and S-G2 transit rates were estimated by means of a 3(H)TdR double labelling technique, and the mitotic rate by use of colcemid. The 3(H)TdR labelling index was also measured. To examine the possible influence of the circadian rhythm, all experiments were performed at two different times of the day with high or low rate, respectively, of epidermal cell proliferation. All flux parameters were altered for the whole 7-h period. The relative inhibitory effect of the skin extract was related to the proliferative state of the epidermal cell population. Cell flux at the G1-S transition showed only minor circadian variations, and treatment with skin extract was followed by a relative reduction of cell flux at this transition that was similar at the two times of the day investigated. In contrast, cell flux at the S-G2 transition showed pronounced circadian variations. The effect of the skin extract on cells at this transition was different at the two times in the 24-h period. In general, inhibition expressed as percent of the controls was stronger when the skin extract was given at times when the cell flux was low or decreasing, and vice versa. In spite of the changes in flux values following administration of a skin extract, the 3(H)TdR labelling indices were reduced only after a delay of 10 h, confirming previous results.