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.