Heterogeneity of tumorigenicity phenotype in murine tumors. Characterization of tumor clones isolated from primary 3-methylcholanthrene-induced fibrosarcomas

In this study we have characterized three series of clonal populations isolated from primary murine fibrosarcomas induced with three different doses of the chemical carcinogen, 3-methylcholanthrene (3-MCA). Clones were evaluated fro their in vivo growth rates after transplantation into normal syngeneic animals, and for immunological cross-protection toward clones derived from the same tumor. A pattern of reactivity emerged from these studies which supports, at the single-cell level, existing theories regarding the correlation between the inducing dose of chemical carcinogen and the antigenicity of the resulting tumors. Clones from tumors induced with 10 mg of 3-MCA were found to be less tumorigenic than clones from tumors induced with 5 mg of 3-MCA. The 5-mg clones were in turn less tumorigenic than the 1-mg clones, all of which grew rapidly in normal animals. Related clones from each tumor were found for the most part to be immunologically noncross-reactive with other clones from the same tumor, suggesting that subpopulations of tumor cells expressing different tumor-specific transplantation antigens (TSTAs) may reside within single primary tumors. We have used these observations to formulate an hypothesis for the origin of antigenic heterogeneity in 3-MCA-induced tumors and as the basis for a discussion of the relationship between cell transformation and the appearance at the cell surface of tumor-specific transplantation antigens.