Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis

Abstract

In chemical carcinogenesis, initiation is defined as the exposure of a tissue, generally mouse skin, to a limited dose of carcinogen which by itself does not induce tumours¹. Subsequent treatments, usually by tumour promoters, are required to allow expression of initiation. In the absence of further treatment, the initiated cells are not recognizable by any known biochemical or biological criteria and the tissue itself functions normally. Much research has centred on elucidating the mechanism of initiation^1–3. It seems likely that initiation involves a genetic change in the target cell as its expression after tumour promotion is a permanent characteristic of the tissue, even if many cell generations have elapsed between initiation and promotion⁴. Studies on tissues from patients with familial polyposis coli suggest that the occurrence of initiated cells in these individuals is due to an autosomal dominant gene⁵. Few studies have actually attempted to define the biological nature of the initiating alteration itself. We report here that cells resistant to terminal differentiation can be readily isolated from skin of BALB/c mice exposed to an initiating dose of carcinogen in vivo but not from control mouse skin. Also, we found that one strain of mouse (SENCAR) might contain a preexisting population of cells resistant to differentiation, and possibly initiated for tumorigenesis.