Effects of methylcholanthrene on epidermal growth regulators. II. Variations in the S-factor.

There is increasing evidence to support the existence of tissue-specific growth-inhibitory chemical substances which can be found in extract homogenized cells. In the epidermis, two such tissue-specific factors (which also have cell-cycle specificity) have been 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 described in a previous paper. Hairless mice received a single topical application of 0.2 ml 0.5% solution of the carcinogen. The short time effect of the carcinogen application on epidermal DNA synthesis was first studied. Other groups of carcinogen-treated mice were then 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 first 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 first and maximum peak on day 2, and a smaller peak on day 8 after treatment. The second experiment showed that the content of G1 chalone in the skins of treated animals varied inversely to the alterations in epidermal DNA synthesis, revealing almost no chalone activity on day 2, and reduced chalone activity on day 8.