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Effects of Epidermal Chalone and Epidermal Growth Factor on a Transplantable Epidermal Carcinoma (Hewitt) of the Mouse in Vivo

German Cancer Research Center, Institute of Biochemistry, Im Neuenheimer Feld 280, D-6900 Heidelberg, Germany

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.

¹ To whom requests for reprints should be addressed.

Received 6/16/78. Accepted 9/27/78.