Effects of mutagens on the immunogenicity of tumor cells: comparison of cell surface changes induced by 5-azacytidine and N-methyl-N'-nitro-N-nitrosoguanidine.

The reduced tumorigenicity of mutagenized cells appears to be due to the induction or alteration of cellular determinants leading to a more effective immune recognition. We previously reported that clones of the murine T-lymphoma Eb obtained after N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) treatment (Eb-MNNG) show a moderate to strong decrease in tumorigenicity and in addition altered expression of several cell surface proteins. We report here that treatment of Eb cells with 5-azacytidine (5-Aza) induces cell surface changes that are very similar to those seen in MNNG clones; likewise, Eb-5-Aza clones were decreased in tumorigenicity and increased in immunogenicity. Regressor mice that had been inoculated with Eb-5-Aza or Eb-MNNG cells could be shown to be protected against a subsequent challenge of Eb cells but not against the syngeneic mastocytoma P 815. Analysis of cytosine methylation of Eb-MNNG and Eb-5-Aza clones by high pressure liquid chromatography revealed decreased levels of methylcytosine content in several clones. Because of these similarities and because both drugs are DNA hypomethylating and gene inducing agents we assume that hypomethylation is involved in causing amplified protein expression. The possible role of amplified proteins in increased immunogenicity is discussed.