Histological changes in TSH-dependent tumours of the thyroid gland during serial transplantation in Fischer 344 rats

Transplantable tumours were induced in the thyroids of Fischer 344 rats fed thiouracil (TU) in a moderately low iodine diet for 8-13 months. Pieces of hyperplastic thyroid were implanted subcutaneously into rats fed a TU containing diet. Almost all implants gave rise to very small vascularized transplants but there were three significantly larger, pieces of which were transplanted again and gave rise to the tumour lines. From the third transplantation generation on, pieces of tumours were implanted into rats treated to have elevated circulating thyrotropin and a group fed a high iodine diet. With some exceptions, the implants grew only in rats fed the TU or a low iodine diet and yielded TSH-dependent tumours. Almost all the tumours observed initially were papillary, and most of the remainder had colloid-filled follicles bounded by columnar cells. One line of tumours was of the latter type for eight generations. The others had more complex histories, in which there were sublines that were papillary for eight or nine generations, whereas, others became progressively more cellular or follicular, and more heterogeneous with respect to histological types present per section at rates that varied with the subline. The large number of population doublings necessary to make a one gram tumour from a single original tumour cell indicates that the cells of dependent papillary tumours were immortalized.