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Immunology of Spontaneous Mammary Carcinomas in Mice

III. Immunogenicity of C3H Preneoplastic Hyperplastic Alveolar Nodules in C3Hf Hosts¹

Department of Bacteriology and Immunology, and Cancer Research Genetics Laboratory, University of California, Berkeley, California

A study was undertaken to determine whether the preneoplastic hyperplastic alveolar nodules of the mammary glands of C3H/Crgl and C3Hf/Crgl mice possess unique antigenic characteristics and whether a previous experience with the nodular tissues can bestow on isogenic animals a degree of heightened reactivity to later challenge with implants of mammary carcinomas arising spontaneously from the nodule outgrowths.

It was found that the C3Hf animals, which were free of biologically active mammary tumor virus, accepted grafts of a C3Hf nodular outgrowth with no evidence of rejection but reacted strongly against implants of either of 2 nodular outgrowths recently derived from the MTV^3-containing, isogenic C3H donors. The reaction against the C3H nodular tissue was much more pronounced in adult than in young C3Hf hosts.

A large proportion of C3Hf females immunized with C3H nodular tissue in adulthood proved to be resistant to subsequent challenge with implants of a mammary tumor that had developed from that outgrowth. In contrast, C3Hf females immunized with a C3Hf nodular outgrowth did not acquire heightened resistance against challenge with 2 mammary tumors originating in the C3Hf outgrowth.

It does not appear possible to explain these findings on the basis of a residual heterozygosis of isoantigenic characteristics between the C3H and C3Hf sublines. The results suggest that immunogenicity of spontaneous mammary carcinomas of mice, and of the preneoplastic nodular tissue, may reside at least partly in antigens possessed by, or induced by, the mammary tumor virus.

¹ This work was supported by Research Grants E-292 and E-344 from the American Cancer Society, Inc., and AI-2309 and CA-05388 from the USPHS, and by Cancer Research Funds of the University of California.

³ The following abbreviations are used: MTV, mammary tumor virus; HAN, hyperplastic alveolar nodule; MER, methanolinsoluble residue.

² Damon Runyon Memorial Postdoctoral Fellow, 1963–1965.

Received 3/25/65. Revised 9/ 7/65.