Relationship between differentiation and carcinogenesis.

Carcinomas are caricatures of the normal process of tissue renerwal. Malignant stem cells proliferate, and some of their progeny differentiati and form benign functional cells. In teratocarcinoma, it has been demonstrated that the stem cells are the target in carcinogenesis and become malignant stem cells. The normal and malignant stem cells are equally differentiated. Normal stem cells of breast and colon are no more differentiated than their counterparts. If they are the target in carcinogenesis, then the concept of dedifferentiation is bypassed as an explanation for the undifferentiated appearance of tumors. While the focus of this meeting has been on mutation as an explanation for carcinogenesis, in this paper emphasis is placed on electrophilic carcinogens acting on cytoplasmic molecules that control gene expression. A type of gene control in addition to the operon is postulated.