methylthiouracil and Hyperplasia

The proliferation kinetics and DNA content of thyroid follicular cells in rats were studied by autoradiography and cytophotometry. Continuous treatment of animals with methylthiouracil (MTU) results in hyperplasia followed by tumour growth in the thyroid gland. The mitotic index (MI) increases from 0.006 +/- 0.002% in controls to 0.13 +/- 0.06% in hyperplasia and to 0.09 +/- 0.03% in malignant cells. The same is true for the labelling index (LI) which rises from 0.08 +/- 0.003% in controls to 1.4 +/- 1.1% in hyperplasia and to 1.0 +/- 0.6% in follicular adenomas. The S-phase duration (TS) is shortened from 8.0 +/- 1.2 hr in controls to 6.0 +/- 1.4 hr in animals treated for 9 months with MTU and prolonged to 15.4 +/- 2.1 hr in papillary carcinomas. In all MTU-treated animals a decrease in the value of the potential population doubling time (TPD) and thyroid weight doubling time (TD) was observed. The cell loss factor (phi) decreases in animals treated for 3 months with MTU and increases during the stage of tumour growth in the gland (animals treated 12-15 months with MTU). DNA measurements in the nuclei of hyperplastic and neoplastic thyroid tissues reveal cells with values exceeding that in control animals. However, no difference was found in the DNA content between thyroid adenomas and carcinomas, nor between thyroid hyperplasia and neoplasia.

Topics: Adenoma; Animals; Carcinoma; DNA; Hyperplasia; Interphase; Kinetics; Male; Methylthiouracil; Mitotic Index; Neoplasms, Experimental; Organ Size; Rats; Thyroid Gland; Thyroid Neoplasms; Time Factors

The influence of hypophysectomy, triiodothyronine (T3), and thyroxine (T4) on the goitrogenic and tumorigenic activity of methylthiouracil (MTU) and 1-methyl-2-mercapto imidazol (MMI) was studied in rats. Hypophysectomy effectively prevented the development of thyroid hyperplasia and adenomas in MTU-treated animals. T3 reduced or abolished the weight loss of goitrogen-treated animals, and prevented the development of thyroid hyperplasia, adenomas, and pulmonary metastatic nodules. The effect of T4 was less pronounced, especially in MTU-treated animals. This hormone failed to neutralize the goitrogenic effect of MTU but it did reduce significantly the incidence of thyroid adenomas and prevented the appearance of pulmonary lesions. The biological effect of the thyroid hormones correlated with their effect on the serum levels of TSH, T3, and T4. The observations are compatible with the assumption that the tumorigenic effect of the two goitrogens depends upon a state of imbalance between TSH and T3.

Topics: Adenoma; Adrenal Glands; Animals; Body Weight; Drug Combinations; Hyperplasia; Hypophysectomy; Imidazoles; Methylthiouracil; Neoplasms, Experimental; Organ Size; Pituitary Gland; Rats; Rats, Inbred Strains; Thyroid Neoplasms; Thyrotropin; Thyroxine; Triiodothyronine

Changes in ornithine decarboxylase (ODC) activity and in polyamine contents of the rat thyroid were studied under various experimental conditions. Methylthiouracil (MTU) treatment produced several-fold increases in the thyroid ODC activity and in the content of putrescine, spermidine and spermine within a week. While serum thyrotropin (TSH) levels increased gradually up to 3 weeks, the content of both putrescine and spermidine tended to reach a plateau after 2 weeks of the goitrogen treatment; spermine content continued to increase progressively for 3 weeks. Discontinuance of MTU at 7 days resulted in a rapid decline in the elevated thyroid ODC activity, followed by a diminution of putrescine, spermidine and RNA contents. Thyroidal putrescine, spermidine and RNA responded more sensitively to both introduction and withdrawal of TSH stimulation than thyroidal spermine and DNA. Excess iodide, having no effect on the basal level of thyroid ODC, suppressed the MTU-induced increase in this enzyme activity without affecting circulating TSH, thyroxine (T4) and triiodothyronine (T3) levels. There was a significant negative correlation between the ODC activity and intrathyroidal concentration of iodine in MTU-pretreated rats. Theophylline increased the thyroid weight and ODC activity when given to rats fed with a subeffective dose of MTU. Analyses of serum TSH, T4, T3 and of thyroidal iodine revealed that TSH-induced thyroid ODC activity was suppressed by increased circulating thyroid hormones and/or intrathyroidal iodine. Furthermore, it was suggested that thyroid hormones and excess iodide acted directly on the thyroid to alter polyamine biosynthesis, possibly by changing the responsiveness of the gland to TSH.

Topics: Animals; Carboxy-Lyases; Glucosephosphate Dehydrogenase; Hyperplasia; Iodides; Male; Methylthiouracil; Ornithine Decarboxylase; Polyamines; Potassium Iodide; Rats; Theophylline; Thyroid Gland

The nature of tumors appearing in the thyroid gland and in the lungs of mice fed two standard goitrogenic drugs (MTU and MII) has been studied. These tumors have been considered malignant on the basis of their morphological appearance and their occurrence in abnormal locations. Some investigatiors, however, have questioned that they are actually malignant. The present results indicate that these tumors are most likely not malignant even if it is shown that the pulmonary nodules are of thyroid origin. The thyroid adenomas disappear once the goitrogen is withdrawn, but thryoid enlargement pesists, and event 6 months after discontinuation of the goitrogenic treatment , pulmonary nodules are still produced. Evidence is presented that these nodules are emoli from hyperplastic thyroid tissue and not tumors.

Topics: Adenoma; Animals; Carcinoma, Hepatocellular; Diet; Glycolysis; Hyperplasia; Iodine; Liver Neoplasms; Lung Neoplasms; Male; Methimazole; Methylthiouracil; Mice; Mice, Inbred Strains; Oxygen Consumption; Thyroid Gland; Thyroid Neoplasms

In the control animals of thyroid peroxidase is localized within the membrane of rough endoplasmic reticulum, perinuclear cisternae, microvilli, lamellar structures of the GOLGI apparatus and dispersed through the cytoplasm small vesicles. 3 weeks treatment of the animals with MTU leads to disappearance of the peroxidase activity from the follicular cells. However, a prolongation of MTU administration until the 6th month and latter causes a reappearance of the peroxidase activity within the same structures of the proliferating cells as in the control animals. In the epithelial cells of follicular and papillary carcinomas the reaction product is observed predominantly within the membrane of the rough endoplasmic reticulum, perinuclear space and outher membrane of the microvilli. The changes in the inhibitory effect of MTU on the peroxidase activity during thyroid carcinogenesis are discussed.

Topics: Animals; Hyperplasia; Male; Methylthiouracil; Microscopy, Electron; Peroxidases; Rats; Subcellular Fractions; Thyroid Gland; Thyroid Neoplasms

Nuclear DNA content was measured in 3 normal, 9 hyperplastic and 16 neoplastic rat thyroid glands. Thyroid hyperplasia and tumor growth were induced after treatment of the animals with X-rays and methylthiouracil. In the control animals only diploid thyroid epithelial cells were observed. At the stages of diffuse and nodular thyroid hyperplasia, the total DNA content per nucleus indicated for a diploid chromosome number and only a few cells were hyperdiploid. In the thyroid adenomas and carcinomas a scattering of the diploid region and an increase in the number of hyperdiploid cells was found. Among the various types of thyroid tumors neither difference in the number of hyperdiploid cells, nor typical pattern of distribution of these cells in the histogram was found. The increased number of hyperdiploid cells in the hyperplastic and neoplastic thyroids suggest an increase in the proportion of the cells entering the cell cycle and does not indicate for appearance of a neoplastic stemline.

Topics: Adenocarcinoma; Adenoma; Animals; Carcinoma, Papillary; Cell Nucleus; Cystadenoma; DNA; DNA, Neoplasm; Epithelium; Hyperplasia; Male; Methylthiouracil; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Rats; Thyroid Gland; Thyroid Neoplasms

The method is based on the cytospectrophotometric estimation of the histochemical reaction to alkaline phosphatase in the gland capillary and on determination of the relative volume occupied by the functioning capillaries. A model experiment under conditions of hyperplasia and hypoplasia of the organ has shown considerable differences in the gland blood supply. Under these conditions the changes of the functioning capillary bed were more pronounced than those of the organ mass.

Topics: Alkaline Phosphatase; Animals; Capillaries; Histocytochemistry; Hyperplasia; Male; Methylthiouracil; Rats; Spectrophotometry; Thyroid Gland; Thyroxine

Topics: Animals; Carcinoma; Carcinoma, Papillary; Cell Nucleus; Cell Transformation, Neoplastic; Chromatin; DNA; Epithelial Cells; Epithelium; Hyperplasia; Male; Methylthiouracil; Microscopy, Phase-Contrast; Rats; Spectrophotometry; Staining and Labeling; Thyroid Neoplasms; Time Factors

Topics: Animals; Drug Interactions; Female; Hyperplasia; Isoniazid; Lung Neoplasms; Male; Methylthiouracil; Mice; Mice, Inbred CBA; Mice, Inbred Strains; Neoplasms, Experimental; Thyroid Diseases

Topics: Animals; Female; Histocytochemistry; Hyperplasia; Methylthiouracil; Microscopy, Electron; Mitochondria; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Succinate Dehydrogenase; Thyroid Neoplasms

Topics: Adenoma; Animals; Antigens, Neoplasm; Cell Transformation, Neoplastic; Cystadenoma; Female; Fluorescent Antibody Technique; Hyperplasia; Methylthiouracil; Microsomes; Neoplasms, Experimental; Organ Specificity; Rats; Thyroid Neoplasms

Topics: Adenocarcinoma; Adenoma; Animals; Female; Golgi Apparatus; Hyperplasia; Methylthiouracil; Microscopy, Electron; Neoplasms, Experimental; Rats; Thyroid Neoplasms

Topics: Adenocarcinoma; Adenoma; Animals; Cell Nucleolus; Cell Nucleus; Golgi Apparatus; Hyperplasia; Methods; Methylthiouracil; Microscopy, Electron; Mitochondria; Neoplasms, Experimental; Organoids; Rats; Ribosomes; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Time Factors

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

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

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