A 6-thioguanine-resistant variant of the 13762 cell line which is no longer tumorigenic or metastatic.

A 6-thioguanine resistant (TGR) variant of the highly tumorigenic and metastatic mammary adenocarcinoma cell line 13762 was obtained. This variant was no longer tumorigenic or metastatic in normal syngeneic rats but did grow as a primary tumor in irradiated animals. Our results suggest that the TGR cell line was rejected by an irradiation-sensitive immunological mechanism. Although the TGR cells produced primary tumors in irradiated animals, there was no evidence of the extensive metastasis seen with the 13762 cells. This apparent inability to metastasize was confirmed by injecting the TGR cells intravenously. Whereas the 13762 cells produced large numbers of metastatic lung foci, there was no evidence of lung metastasis with the TGR cells, even in irradiated animals. Revertant cells for the 6-thioguanine-resistant phenotype were still non-tumorigenic and non-metastatic in normal rats, suggesting that 6-thioguanine resistance is not associated with the altered tumorigenic phenotype. From the TGR variant, cell lines were selected with an increased ability to produce tumors in normal rats. Although some of these revertants were capable of producing limited lung metastases in normal animals, extensive metastases were always seen when the cells were injected into irradiated animals. Differences between the 13762 and the TGR variants were also found in their ability to produce plasminogen activator. The TGR cells released far less plasminogen activator in culture than the 13762 cells. This could be a contributing factor in their different metastatic potentials.