Tumor cell variants obtained by mutagenesis of a Lewis lung carcinoma cell line: immune rejection by syngeneic mice

Abstract

It has been reported that, by mutagenesis of a malignant mouse teratocarcinoma cell line, it is possible to obtain cell variants that are incapable of forming progressive tumors in syngeneic mice. These variants, which were called "tum-," are eliminated from the host by an immune rejection process. We report here that similar variant cell clones can be obtained at high frequency from a Lewis lung carcinoma cell line treated with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine. Syngeneic C57BL/6 mice reject these tum- clones and acquire a strong radioresistant immune protection against the immunizing clone. When the challenging tum- clone differs from the immunizing clone, a weaker radioresistant immune protection can be demonstrated with some, but not all, combinations. All the tum- clones induce a significant protection against the original Lewis lung malignant cells. These results imply that each Lewis lung tum- variant carries on its surface a singular antigen in addition to one or more weak antigens already present on the original tumor cell line. This antigenic pattern is similar to that found on teratocarcinoma tum- variants. Our results suggest that the procedure of using a mutagen in order to generate tum- variants carrying new transplantation antigens may be generally applicable to cancer cells.