Fast onset of DNA synthesis stimulated by tumor promotor in mouse epidermis at the initation stage of carcinogenesis.

Abstract

Mouse skin was treated with 7,12- dimethylbenz[a]anthracene (DMBA), benzo[a] pyrene (BP), or urethan. After 5 weeks, on the same region of skin, 0.5, 0.1, or 0.02% croton oil was applied. 3H-thymidine (3H-TDR) was injected every 4th hour during a 20- to 24-hour period after application of croton oil. The labeling index in interfollicular epidermis was determined autoradiographically. Croton oil induced transition to the DNA synthesis phase in most basal cells. The mean time between application of croton oil and transition of basal cells to the DNA synthesis phase was significantly shorter in DMBA-“initiated” epidermis than in normal epidermis for 3 concentrations of croton oil. The labeling index for mature cells also increased more rapidly, in epidermis treated with initiator. The difference between normal and initiated epidermis was most pronounced after 0.1% croton oil was applied. With this concentration, initiation with BP and urethan also shortened the time between stimulation and onset of DNA synthesis. Without stimulation, the labeling index curves for basal cells did not differ in normal and initiated epidermis on repeated injections of 3H-TDR. Fast onset of stimulated DNA synthesis possibly is characteristic of epidermis treated with initiators and results from increased sensitivity of the genome to tumor promoters.