Appearance of serum antibodies to rat yolk-sac carcinomas during the latent period prior to primary tumor development.

Rat yolk-sac tumors were induced by intraperitoneal (i.p.) displacement of the visceral yolk sac in fetectomized W/Fu rats. Serum was obtained from each female rat prior to the pregnancy preceding the tumor-inducing procedure and then once a month during the induction period. The sera were analyzed for the presence of antibodies binding to cultured cells of one of the yolk-sac tumors. Sera were also assayed for complement-dependent cytotoxic antibodies on tumor cells. In rats that developed tumors, antibodies reacting specifically with the target tumor cells could be detected in all of 10 rats. Antibodies appeared before tumor detection in all animals but one, and in 6 rats as early as 11 to 25 weeks prior to tumor detection. Nine rats developed antibodies demonstrable in the binding assay and in 6 of those the antibodies appeared 8 to 25 weeks before the tumor became palpable. Analysis of the isotypes of the Ig that bound to tumor cells showed that IgG1 and IgG2b were most frequently present. In one rat IgG2a antibodies appeared one month before tumor detection followed by IgG1 and IgG2b antibodies detectable 4 weeks later. IgG2c and IgM antibodies were not detected in any of the rats. At dilution 1/10, sera of all 10 rats showed specific cytotoxicity to the tumor cells in the presence of added rabbit complement. In 9 of these animals antibodies were demonstrated 1 to 4 months prior to tumor detection.