thiouracil and Hyperplasia

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.

Topics: Animals; Carcinogens; Cell Transformation, Neoplastic; Female; Hyperplasia; Male; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Neovascularization, Pathologic; Pedigree; Rats; Rats, Inbred F344; Thiouracil; Thyroid Gland; Thyroid Neoplasms; Thyrotropin

Membrane-bounded fragments of thyroid epithelial cells are found in the lumen of the thyroid follicle at early stages of involution of the hyperplastic gland. To demonstrate this, thyroid glands were made hyperplastic by feeding rats a low iodine diet containing thiouracil for 3 weeks. Involution was induced by the feeding of a high iodine diet. Three types of dense cell fragments were observed in the lumen at its periphery within 5 hours after the change of diet: (1) single, relatively large fragments that contained vesicles occasionally, (2) a cluster of rounded fragments of relatively small size. Some of these had a narrow tail, and (3) elongated narrow fragments in a row parallel to the apical surface of one or more epithelial cells. The fragments are probably derived from the thyroid epithelial cells since no other cell types were generally present. By 14 hours the fragments were distributed randomly throughout the lumen. Fragments were no longer present by 12 days of involution in most follicles. Fragment formation may be a mechanism for disposal of excess plasma membrane deposited by exocytic vesicles during rapid secretion of thyroglobulin into the follicular lumen early in involution.

Topics: Animals; Cell Membrane; Diet; Endocytosis; Epithelium; Hyperplasia; Iodine; Male; Microvilli; Rats; Thiouracil; Thyroid Gland

Topics: Adipose Tissue; Animals; Capillaries; Hyperplasia; Lipolysis; Male; Mitosis; Rats; Rats, Inbred F344; Thiouracil; Thyroid Gland

Topics: Animals; Capillaries; Cell Division; Cell Membrane; Cytoplasm; Cytoskeleton; Endothelium; Hyperplasia; Intercellular Junctions; Kinetics; Male; Microvilli; Rats; Telophase; Thiouracil; Thyroid Gland

Topics: Animals; Blood Platelets; Capillaries; Cell Membrane; Collagen; Endothelium; Hyperplasia; Male; Microscopy, Electron; Platelet Aggregation; Rats; Thiouracil; Thyroid Gland

Kinetics of accumulation of radioiodine was studied in thyroids of chickens before, during, and following ingestion of 0.25% thiouracil (TU). After a latent period of about 5 days, weight of the thyroid gland increased, reaching its maximum (42 mg/100 g body wt) after 21 days of TU ingestion; thyroid weight decreased immediately on withdrawal of TU but tended to plateau at a higher level than that of controls. One-way clearance increased by day 4 of ingestion of TU and reached its peak early during hyperplasia; it very quickly reverted to a control level on withdrawal of TU. Exit-rate constant increased markedly during early hyperplasia and decreased to a level less than normal after withdrawal of TU. Concentration of 127I decreased by a factor of 18 by 2 wk of feeding TU; it increased to practically a normal level by 1 wk after withdrawal of TU.

Topics: Animals; Hyperplasia; Iodides; Iodine Radioisotopes; Kinetics; Thiouracil; Thyroid Function Tests; Thyroid Gland

Young adult male Fischer rats were fed 0.25% thouracil in a low-iodine diet to produce hyperplasia of the thyroid gland. The capsule of the thyroid gland increased in thickness from approximately one cell in controls to a substantial multilayered structure. Increase in capsule thickness was noted by 3 days. The cell population of the capsule was largely fibroblasts, but during a period within the interval from 14 to 28 days, the capsule tended to be exceptionally thick and contained many mononuclear leukocytes. At later times the capsule was not quite as thick and the leukocytes largely disapproved. Capillaries developed in the capsule probably by sprouting. The capsule growth was so extensive that certain neighboring tissues were often incorporated into the capsule, including arteries, veins, nerves, striated muscle, and lymph nodes. There was some regional specificity in the development of capsular hyperplasia. Connective tissue increased around the thyroid and parathyroid glands but not between them. Connective tissue in partitions with the thyroid gland also increased in thickness, although the extent of accumulation of cells and intercellular matrix was much less than in the capsule.

Topics: Animals; Blood Vessels; Connective Tissue; Fibroblasts; Hyperplasia; Leukocytes; Lymphatic System; Male; Rats; Thiouracil; Thyroid Diseases; Thyroid Gland

To study blood capillary growth in the hyperplastic thyroid gland, rats were fed 0.25% thiouracil in a low iodine diet for time intervals up to 100 days. Thyroids were fixed by vascular perfusion and embeded in Epon. Whole lobes were sectioned from pole to pole and slides were prepared of sections every 0.3 mm. Capillaries were clearly enlarged by 3 days and they enlarged progressively thereafter. By 3 days, the cells of many neighboring capillaries came into close apposition and from this time on, there was evidence of fusion of capillary walls in the form of partial septa in the capillary lumens. Fusion continued until 20 days, when follicles were almost completely surrounded by a continuous endothelial sheet and unfused capillary walls were separated by connective tissue. The vascular pattern around peripheral follicles changed in a way similar to interior follicles, except that in places, capillaries were gradually excluded from the space between epithelium and thyroid capsule. Vascular enlargement was restricted to the thyroid blood vessels. There was no obvious enlargement of the blood capillaries of the parathyroid despite its close proximity to the thyroid.

Topics: Animals; Capillaries; Hyperplasia; Male; Rats; Thiouracil; Thyroid Gland

Topics: Animals; Cell Adhesion; Cytoskeleton; Epithelial Cells; Epithelium; Erythrocytes; Hyperplasia; In Vitro Techniques; Male; Phagocytosis; Pseudopodia; Rats; Thiouracil; Thyroid Gland

A microhemorrhagic process was consistently observed in association with the induction of thyroid hyperplasia by dietary thiouracil in the rat. This process appeared to involve the extravasation of erythrocytes (RBCs) through hyperplastic capillary walls. Those sites of extravasation which were directly visualized involved endothelial openings of less than 1 mu. These openings were surrounded by endothelial cytoplasm containing a dense fibrous material and were associated with RBC constriction during passage. Extravasated RBCs were most often noted singly or in small groups, either in columns between follicular epithelial cells or embedded amongst the basal epithelial infoldings. Occasionally, extravasated RBCs were also observed within follicular lumens. Extravasated RBCs were usually intact ultrastructurally, but occasionally an apparent hemolytic process was observed, both for RBCs embedded amongst epithelial cells and for those within follicular lumens. The nature and etiology of this microhemorrhagic process are considered in relation to the hypervascularity of the gland, the possibility of capillary wall alterations, the presence of endothelial cell mitoses, and the localization of the process.

Topics: Animals; Epithelium; Erythrocytes; Hemolysis; Hemorrhage; Hyperplasia; Male; Rats; Thiouracil; Thyroid Diseases; Time Factors

Topics: Administration, Oral; Animal Feed; Animals; Cestode Infections; Chickens; Hemoglobins; Hyperplasia; Hypertrophy; Hypothyroidism; Leukocyte Count; Lipids; Poultry Diseases; Thiouracil; Thyroid Gland

Topics: Animals; Diet; DNA; Hyperplasia; Iodine; Male; Mice; Organ Size; Polyploidy; Rats; Thiouracil; Thyroid Diseases; Thyroid Gland

Topics: Angiography; Animals; Contrast Media; Depression, Chemical; Drug Synergism; Hyperplasia; Iodine; Male; Rats; Thiouracil; Thyroid Gland; Thyroxine

Topics: Anemia, Hemolytic; Animals; Animals, Laboratory; Body Weight; Dogs; Female; Haplorhini; Hyperplasia; Male; Mice; Microscopy, Electron; Pigmentation; Rats; Tetracycline; Thiouracil; Thyroid Gland

Topics: Animals; Colloids; Cortisone; Cricetinae; Goiter; Hyperplasia; Hyperthyroidism; Iodine; Pharmacology; Research; Sulfadiazine; Thiocyanates; Thiouracil; Thyroiditis; Triiodothyronine

Topics: Acetylcholine; Animals; Cholinergic Agents; Cholinesterase Inhibitors; Female; Goiter; Hyperplasia; Neoplasms; Neostigmine; Pregnancy; Pregnancy Complications; Rats; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Disease; Hyperplasia; Hypertrophy; Thiouracil; Thyroid Diseases; Thyroid Gland

Topics: Cystine; Dimercaprol; Goiter; Hyperplasia; Hypertrophy; Methionine; Methylthiouracil; Pharmaceutical Preparations; Thiouracil; Thyroid Gland; Viscera

Topics: Cystine; Dimercaprol; Goiter; Hyperplasia; Hypertrophy; Methionine; Methylthiouracil; Thiouracil

Topics: Disease; Female; Goiter; Humans; Hyperplasia; Infant; Infant, Newborn; Infant, Newborn, Diseases; Iodides; Iodine; Mothers; Pregnancy; Thiouracil; Thyroid Diseases; Thyroid Gland

Topics: Guinea Pigs; Hyperplasia; Iodides; Iodine; Iodine Radioisotopes; Propylthiouracil; Thiouracil; Thyroid Gland

Topics: Humans; Hyperplasia; Liver Diseases; Thiouracil; Thiourea; Thyroid Gland

Topics: Animals; Fibrous Dysplasia of Bone; Hyperplasia; Osteitis; Parathyroid Diseases; Parathyroid Glands; Rats; Thiouracil; Thiourea

Topics: Animals; Hyperplasia; Rats; Thiouracil; Thiourea; Thyroid Diseases

Topics: Animals; Hyperplasia; Macaca mulatta; Thiouracil; Thyroid Gland

Topics: Carcinoma; Hyperplasia; Hyperthyroidism; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Goiter; Hyperplasia; Methylthiouracil; Pharmaceutical Preparations; Thiouracil; Thiourea; Thyroid Gland