Multiple antigenic specificities within primary 3-methylcholanthrene-induced rat sarcomas and metastases

Sarcomas were induced in WAB/Not rats by subcutaneous injection of 10, 5 or 1 mg 3-methylcholanthrene (MCA) but not by 0.1 mg. Although tumours appeared earlier in rats given 10 mg MCA, compared with 1 mg, the majority of transplant lines from primary tumours were immunogenic and there was no correlation between the inducing dose of carcinogen and the growth characteristics or immunogenicities of the transplant lines. Most importantly sublines established from opposite poles of primary sarcomas were antigenically distinct in a substantial portion of cases, indicating that the primary tumours consisted of antigenically heterogeneous populations of cells. Furthermore, with one rat, renal and pulmonary metastases were antigenically distinct from a peritoneal secondary and the primary growth. These findings indicate that primary carcinogen-induced tumours may be polyclonal in origin and this has implications for both the understanding of the carcinogenic process, and for the immunotherapy of malignant disease.