Regenerative proliferation of mouse epidermal cells following application of a carcinogenic skin irritant (MCA)

Summary

0.025 ml of a 1% solution of the complete skin carcinogen 20-methylcholanthrene (MCA) dissolved in benzene was applied to the back skin of hairless mice. At different time intervals up to 3 days after the carcinogen application groups of animals were injected i.p. with 30 μCi³H-TdR 30 min before they were killed. Single cell suspensions of epidermal basal cells were prepared by a combined enzymatic and mechanical separation method, and the DNA frequency distribution pattern from each cell suspension was measured by means of micro-flow fluorometry. Smears for autoradiography were made from each cell suspension and the labeling index and mean grain count assessed.

After a short initial delay, MCA induced an increase in the labeling index similar to that observed after non-specific cell injury and cell loss. Thereafter, the cells were considerably delayed in their progression through the S phase, with a low exit from S resulting in a transient emptying of the G₂ compartment, without indications of any significant delay of the passage through G₂ phase. The cells that had been injured by the MCA application in or just before the S phase proceeded into the G₂ phase and mitosis more than 24 h after the initiation of DNA synthesis. The cell kinetic reaction of epidermis to a single application of MCA is thus very different from that caused by a nonspecific cell damage, e.g. application of the vesicant agent cantharidin or removal of surface cells by cellophane tape stripping.