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Soluble Microsomal Antigens of Normal and Preneoplastic Livers¹

Max-Planck-Institut für Virusforschung, Tübingen, Germany, and The Institute for Cancer Research, Fox Chase, Philadelphia, Pennsylvania 19111

At least 8 macromolecules in the supernatant fraction of rat liver immunologically cross-react with antigens extracted from liver microsomes. These supernatant analogs of microsomal antigens have been resolved by extensive column electrophoresis and differentially characterized. One species () is highly acidic, 3 (ß, ₁, and ₂) are of intermediate acidity, and 4 (, ₁, ₂, and ) are near-neutral. The ß is identical or closely related to the tissue-specific microsomal antigen, which others have found to be diminished in preneoplastic liver and absent from liver tumors induced by azocarcinogen and sometimes by N-2-fluorenylacetamide. Feeding these carcinogens, or in certain cases the control diets, affects the levels of individual supernatant analogs.

The principal soluble protein conjugates of these carcinogens present in preneoplastic livers do not cross-react with these microsomal antigens. Also, the conjugates and the coexistent supernatant analogs of the microsomal antigens differ electrophoretically. All appear to be unrelated. Thus, azo and fluorenyl carcinogen metabolites appear not to conjugate with these microsomal antigens or their supernatant counterparts. The findings do not support postulation of an immunologic sequence of cancer causation that is based on conjugation of carcinogen with the principal tissue-specific microsomal antigen in preneoplastic liver.

¹ Aided by Grants CA 05945 and CA 06927 from the USPHS, an appropriation from the Commonwealth of Pennsylvania, and Grants E73 and IN 49-E and -F from the American Cancer Society.

Received 4/ 6/65. Accepted 11/ 6/67.