HETEROGENEITY OF TUMORIGENICITY PHENOTYPE IN MURINE TUMORS

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.