Effect of Tumor Promoters on Cell Kinetics in Mouse Epidermis

Abstract

Tumor promoters (Tween-60 and croton oil) were applied on normal mouse skin and skin initiated by 7,12-dimethylbenz[a]anthracene a month previously. The proliferative response in treated epidermis was estimated by the use of autoradiography with ³H-thymidine. The number of cells synthesizing DNA in the basal layer increased 12 hours after application of tumor promoters and was highly elevated for 72 hours. DNA-synthesizing cells also appeared among mature cells. The labeling index for basal cells in initiated epidermis was significantly higher than in normal epidermis 12–16 hours after application of tumor promoters. During the period of active proliferation, the mitotic cycle, as estimated by the method of labeled mitoses, was 10 hours, both in normal and initiated epidermis, i.e., 8 times shorter than in normal, unstimulated epidermis. Cell maturation, as measured by transition of labeled cells from the basal layer into the layer of spinous cells, was accelerated in the epidermis stimulated by tumor promoters. Cell number/1 mm of epidermis did not change significantly during the first hours after application of tumor promoters, but rose thereafter because of elevation in the number of mature cells. This el evation tended to be more pronounced in initiated skin. It is hypothesized that the action of tumor promoters on initiated epidermis leads to the selection of cells with shortened G₁ phase, which may be associated with weakened response to the factors regulating cell proliferation.