The effects of chalone-containing skin preparations and of epidermal growth factor on the proliferative activity of a transplantable nonkeratinizing epidermal carcinoma (Hewitt) of the mouse have been studied in vivo. Whereas crude skin extracts suppressed DNA labeling (probably due to cytotoxic effects), highly enriched epidermal G1 chalone was found to inhibit neither DNA synthesis nor tumor growth. Consequently, repeated injections of the factor did not prolong the survival rate of tumor-bearing animals.
Extracts made from tumor tissue did not show any G1 chalone activity when injected into normal mice, whereas extracts from normal mouse epidermis exhibited a strong inhibitory effect on epidermal DNA labeling. Despite being resistant to epidermal G1 chalone, the carcinoma was found to be susceptible to the antimitotic effects of skin extracts which are most probably due to the epidermal G2 chalone.
A single i.p. injection of epidermal growth factor caused a doubling of DNA labeling in the transplanted tumor.
These observations are consistent with the hypothesis that epidermal G1 chalone controls only the proliferation of epidermal “stem cells” in a rather advanced stage of differentiation, whereas epidermal G2 chalone as well as epidermal growth factor appear to affect more primitive cell types.