Quantitative and molecular comparison of initiation frequency of mammary carcinogenesis by radiation and chemical carcinogens

Mammary carcinogenesis is a multistage process consisting minimally of initiation and promotion/progression steps. In order to enumerate the frequency of initiation, we developed a quantitative clonal mammary transplantation assay. Rats are treated with either radiation or chemical carcinogens such as nitrosomethylurea (NMU) or 7,12-dimethylbenz(a)anthracene (DMBA). One day later these donor rats are killed and the mammary tissue is removed and enzymatically monodispersed. The monodispersed cells are a heterogeneous mixture of epithelial and stromal cells. Within this mixture are mammary epithelial cells that upon transplantation give rise to morphologically and functionally normal mammary tissue. We have demonstrated that such tissue can arise from a single cell. We refer to this cell type as either a mammary clonogen or a stem-like mammary cell.