Studies on the mechanism of skin tumor promotion.

34). Clayson (8) has pointed out that “. . . promoting agents must act by bringing about an increase in the number of precancerous or cancerous cells compared with the number of normal cells. . . .“While this selection for initiated cells may be accomplished in several different ways, a molecular basis for the selection is suggested based on the experiments described here. The process of promotion may involve the genetic expression of modified regions of DNA in the few cells altered critically by the initiating agent followed by the proliferation of these cells into visible tumors (3). The effects of the most commonly used promoting agent, croton oil, on the rates of synthesis of DNA, RNA, and protein in mouse skin were determined. The duration of stimulated macromolecular synthesis was then compared with the time interval between applications of croton oil used as a tumor promoter that resulted in maximal tumor incidence. Cantharidin, a hyperplastic agent, was tested for tumor-promoting activity and for its effect on the rate of DNA synthesis. A comparison was made between the early effects of croton oil and of cantharidin on the rate of synthesis of rapidly labeled RNA fractionated on a methylated albumin Kieselguhr column. The capability of wound healing, a potent local stimulus to mitosis, to promote skin tumor formation was determined after initiation alone and after initiation plus limited treatment with croton oil. The results of these experiments are discussed with regard to the mechanism of skin carcino genesis.