Characteristic complements of nuclear nonhistone proteins in colonic epithelial tumors

Nuclei were isolated from colonic epithelial tumors induced in rats by the administration of 1,2-dimethylhydrazine. The nuclei were fractionated according to buoyant density by centrifugation in discontinuous sucrose density gradients. Nuclei differing in density differ in size, nonhistone protein-to-DNA ratio, and DNA synthetic activity. Their distribution in a density gradient also reflects their histological localization in the layers of the intestinal mucosa, as judged by the nuclear capacity for [3H]thymidine incorporation into DNA in vivo. Different nuclear classes isolated from the tumors contain characteristic complements of nuclear nonhistone proteins. Particularly striking accumulations of two protein classes with molecular weights of ca. 44,000 and 62,000 occur during carcinogenesis. These proteins are not uniformly distributed throughout all nuclear classes derived from the tumors. They are not at all prominent in normal colonic epithelial nuclei or in epithelial cells surroundign the tumors, or in the liver nuclei of animals treated with 1,2-dimethylhydrazine. Procedures for the differential extraction of these protein classes are described. Similar nuclear proteins have been detected in human colonic tumors and in a human cell line (HT-29) derived from an adenocarcinoma of the colon. The selective accumulation of such proteins in colonic tumor nuclei may have diagnostic value.