EFFECTS OF METHYLCHOLANTHRENE ON EPIDERMAL GROWTH-REGULATORS .2. VARIATIONS IN S-FACTOR

There is increasing evidence to support the existence of tissue specific growth inhibitory chemical substances which can be found in aqueous extracts of homogenized cells. In the epidermis, 2 such tissue specific factors (which also have cell cycle specificity) were found. These factors act specifically on different phases of the cell cycle (epidermal G1 and G2 chalones, respectively). This paper concerns a study of the effect of 20-methylcholanthrene on the epidermal G1 chalone. The variations in epidermal G2 inhibitor after such treatment were previously described. Hairless mice received a single topical application of 0.2 ml 0.5% solution of the carcinogen. The short term effect of carcinogen application on epidermal DNA synthesis was studied. Other groups of carcinogen-treated mice were killed at similar time intervals, and the treated area of skin was homogenized and extracted with water. The inhibitory effect of these extracts on normal epidermal G1 cells was assayed in normal hairless mice. The obtained inhibition was registered as an expression of G1 inhibitor concentration in the skin extracts. The 1st experiment confirmed that a single carcinogen application provokes a short block in epidermal DNA synthesis, followed by a high, biomodal peak of increased activity with the 1st and maximum peak on day 2, and a smaller peak on day 8 after treatment. The 2nd experiment showed that the content of G1 chalone in the skin of treated animals varied inversely with alterations in epidermal DNA synthesis, revealing almost no chalone activity on day 2, and reduced chalone activity on day 8. Different explanations of these results are discussed. Carcinogen application injures and kills epidermal cells with subsequent alterations in the content of G1 chalone in the skin. This theory may explain the changes observed in the labeling indices. The effects of methylcholanthrene on the amount of G1 chalone in the skin are probably related to the direct, toxic, cell killing effect of the carcinogen, and not connected with the specific carcinogenic potency of methylcholanthrene.