Incorporation of carbohydrates into abnormal thyroglobulin in an experimental rat thyroid tumor.

Previous findings indicated that in line 1–1C2 of experimental rat thyroid tumor there is decreased secretion of 19S thyroglobulin associated with a lack of incorporation of sialic acid into thyroglobulin and sialyltransferase activity in the tumor. In the present work we studied another tumor line, 1–8, in which particle bound iodopro-tein is also increased. This tumor, however, secretes an abnormal form of thyroglobulin. Soluble and digitonin-solubilized iodoproteins were examined in tumor labeled in vitro with N-acetylmannosamine, galactose, mannose, N-acetyl-glucosamine, leucine and iodine. About half of each label except galactose and N-acetyl-mannosamine was in the pellet after digitonin extraction and the remainder was evenly distrib-uted between soluble and solubilized fractions. After galactose labeling, the soluble fraction con-tained relatively more labeled protein; after N-acetylmannosamine, the pellet content was higher but most of the remainder was in the soluble fraction. The soluble and solubilized fractions analyzed by density gradient centrifugation showed one broad radioactive peak in the 7–9S region, which had the same elution volume as normal thyroglobulin in Sephadex G-200. When tested by double immunoprecipitation, up to 49‰ of the total radioactivity in each fraction was related to thyroglobulin. The microsome fraction of the tumor contained a normal amount of sialyltransferase activity specific for thyroglobulin. These findings indicate that tumor line 1–8 synthesizes 7–9S iodoprotein containing all the carbohydrates normally found in thyroglobulin and having immunological properties of 19S thyroglobulin. Taken with earlier studies on tumor line 1–1C, it is evident that cell transformation in the experimental rat thyroid tumors affects thyroglobulin synthesis in several different ways.