methylthiouracil and Thyroid-Neoplasms

Papillary carcinomas of the thyroid gland induced in rats by combined methylthiouracil (MTU)/nitrosomethylurea treatment were studied electron microscopically and histochemically for their acid phosphatase activity, radioactive iodine uptake and for their thyroglobulin synthesis. The papillary carcinomas accumulated radioactive iodine, synthesized thyroglobulin and showed a perinuclear localization of acid phosphatase activity in the cytoplasm. After omitting the reactive thyrotropic effect (cessation of MTU administration) a decrease of both iodine organification and acid phosphatase activity was observed. The synthesis of thyroglobulin was also reduced. The changes in the ultrastructure of tumour cells corresponded to the respective functional activities. The results suggest that the papillary carcinomas may have a functional dependence on thyroid-stimulating hormone.

Topics: Acid Phosphatase; Animals; Autoradiography; Carcinoma, Papillary; Female; Iodine Radioisotopes; Methylnitrosourea; Methylthiouracil; Microscopy, Electron; Rats; Rats, Inbred Strains; Thyroglobulin; Thyroid Neoplasms

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 paper discusses the influence of deranged function of the thyroid (in postnatal period) on the transplacental carcinogenic effect of N-nitrosomethylurea (NMU) in albino noninbred rats. It was found that exogenous thyroxin-induced hyperthyroidism and thyroid function suppression either by long-term treatment with a thyreostatic agent--methylthiouracil (MTU) or thyroidectomy are followed by a lower frequency of, chiefly, nervous system tumors which are typical of NMU-induced transplacental carcinogenesis in rats. Moreover, transplacental treatment with NMU potentiated the carcinogenic effect of MTU on the thyroid. The latter manifested itself in a higher frequency of malignancies of the thyroid in animals exposed to a combined treatment with NMU (transplacentally) and MTU (postnatally) as compared with those given MTU only (postnatally).

Topics: Animals; Brain Neoplasms; Female; Maternal-Fetal Exchange; Methylnitrosourea; Methylthiouracil; Neoplasms, Experimental; Pregnancy; Rats; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy; Thyroxine

Topics: Adenocarcinoma; Adenoma; Animals; Methylthiouracil; Microscopy, Electron, Scanning; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Rats; Thyroid Gland; Thyroid Neoplasms

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

Thyroid adenomas and carcinomas were induced after continuous (12--15 months) treatment of Wistar rats with methylthiouracyl. Ultrastructural cytochemical technique was used in studying the localization of thyroid peroxydase in different follicular cell structures. In control animals, the enzyme was localized on the ER membranes, the internal lamellae of Golgi's apparatus, the perinuclear membrane, the microvilli and in isolated apically arranged lisosomes and microvesicles. No peroxidase activity was detected in animals, having received one-month methylthiouracyl treatment. This was confirmed also by the chromatographic study, showing the presence of inorganic iodine only. Peroxidase activity was demonstrable in only part of the thyroid adenomas and carcinomas; the enzymes was localized in the same subcellular structures as in control animals. In these tumors a variety of iodine-containing components were also identified, largely of the MIT and DIT group.

Topics: Animals; Enzyme Activation; Male; Methylthiouracil; Neoplasms, Experimental; Peroxidases; Rats; Thyroid Gland; Thyroid Neoplasms

Seventy-five female Wistar rats of 150 g each were given 3 X 40 mg/kg body weight nitrosomethylurea (NMU) and 4 weeks later until death (in the 9th-60th week) methylthiouracil (MTU), as a 0.1% solution in their drinking water. After 2 months, in the almost colloid-less thyroid gland individual foci appeared which consisted of sometimes colloid containing follicles with increased cytoplasmic and nuclear basophilia; they increased in number during the subsequent weeks and finally resulted in nodes with different morphologic structures. From the 16th week on there were tumors infiltrating the capsule, and after the 24th week there were angioinvasive carcinomas. Thirteen rats had developed lung metastasization after the 30th week. Cytology could only distinguish between the follicular carcinomas of low differentiation and the follicular adenomas. If these findings are applied to human pathology, one would have to reckon with adenomas which can develop their malignant characteristics without necessarily changing their histologic and cytologic appearance.

Topics: Animals; Female; Lung; Lung Neoplasms; Methylnitrosourea; Methylthiouracil; Neoplasms, Experimental; Nitrosourea Compounds; Rats; Thyroid Gland; Thyroid Neoplasms

Topics: Adenoma; Age Factors; Animals; Body Weight; Carcinoma; Male; Methylthiouracil; Neoplasms, Radiation-Induced; Organ Size; Rats; Thyroid Gland; Thyroid Neoplasms; Time Factors; X-Rays

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

Topics: Animals; Cytodiagnosis; Female; Methylnitrosourea; Methylthiouracil; Neoplasms, Experimental; Rats; Thyroid Neoplasms

Irradiation of the neck region of 10 days old Wistar rats with 300 rads X-rays and their subsequent treatment with MTU leads to the development of thyroid tumors. The ultrastructure of the thyroid tumors induced was studied by transmission (TEM) and scanning electron microscopy (SEM). In follicular carcinomas, cylindrical or high columnar cells with abundant microvilli, well-developed ergastoplasmic reticulum and a hypertrophied Golgi complex predominate. The cytoplasm of the tumor cells of papillary carcinomas was composed of large pleomorphic cisternae, irregular in shape mitochondria, dense bodies, phagolysosomes and lamellar or multivesicular structures. Scanning electron microscopy revealed in the control animals a regular pattern of thyroid follicles tied to each other by tissue bridges and covered by set of blood and lymph vessels. The relief of the follicular carcinomas was irregular indicating follicles different in size and shape. The internal surface of the neoplastic follicles was also irregular as result of deep invaginations and intrafollicular cell growth. The apical region of the normal and neoplastic thyroid follicular cells was covered with abundant microvilli protruding into the colloid.

Topics: Adenocarcinoma; Animals; Carcinoma, Papillary; Male; Methylthiouracil; Microscopy, Electron; Microscopy, Electron, Scanning; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Rats; 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

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: Age Factors; Animals; Cell Differentiation; Cell Nucleus; Cell Transformation, Neoplastic; Embryo, Mammalian; Endoplasmic Reticulum; Female; Histological Techniques; Inclusion Bodies; Lysosomes; Methylthiouracil; Mice; Microscopy; Microscopy, Electron; Mitochondria; Neoplasms; Neoplasms, Experimental; Organoids; Ribosomes; Staining and Labeling; Thyroid Gland; Thyroid Neoplasms

Topics: Adenocarcinoma; Administration, Oral; Animals; Carcinoma; Carcinoma, Papillary; Injections, Intravenous; Methylthiouracil; Neoplasms, Experimental; Nitrosourea Compounds; Rats; Thyroid Neoplasms; Time Factors

Topics: Animals; Methylthiouracil; Nitrosourea Compounds; Rats; Thyroid Neoplasms

Topics: Adenoma; Animals; Antigens, Neoplasm; Cystadenoma; Fluorescent Antibody Technique; Methylthiouracil; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Thyroglobulin; Thyroid Neoplasms

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

Topics: Animals; Antithyroid Agents; Carbimazole; Chromatography, Paper; Chromatography, Thin Layer; Humans; Imidazoles; Male; Methimazole; Methylthiouracil; Propylthiouracil; Rats; Sulfur Isotopes; Thiouracil; Thyroid Gland; Thyroid Neoplasms; Thyroidectomy

Topics: Adenoma; Animals; Body Weight; Cricetinae; Cystadenoma; Female; Iodine Isotopes; Lung Neoplasms; Methylthiouracil; Neoplasms, Experimental; Organ Size; 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: Animals; Autoradiography; Female; Male; Methylthiouracil; Neoplasms, Experimental; Rats; Thyroid Neoplasms

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

Topics: Adenoma; Animals; Antithyroid Agents; Carcinogens; Carcinoma, Hepatocellular; Cysts; Female; Glucose; Goiter; Imidazoles; Kidney Diseases; Lactates; Liver Neoplasms; Male; Methimazole; Methylthiouracil; Mice; Mice, Inbred Strains; Ovarian Cysts; Oxygen Consumption; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Triiodothyronine

Topics: Animals; Autoradiography; Chromatography, Paper; Iodine Radioisotopes; Methylthiouracil; Protein Binding; Rats; Thyroid Function Tests; Thyroid Gland; Thyroid Neoplasms

Topics: Adenoma; Animals; Humans; Methylthiouracil; Microscopy, Electron; Neoplasm Transplantation; Neoplasms, Experimental; Organoids; Rats; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Cell Membrane; Cell Transformation, Neoplastic; Endoplasmic Reticulum; Methylthiouracil; Mitochondria; Neoplasms, Experimental; Rats; Thyroid Neoplasms

Topics: Adenocarcinoma; Animals; Basophils; Female; Hypothyroidism; Liver Neoplasms; Mammary Neoplasms, Experimental; Methylthiouracil; Neoplasms, Experimental; Ovarian Neoplasms; Pituitary Gland; Rats; Thyroid Neoplasms; Thyroidectomy

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: Animals; Benz(a)Anthracenes; Carcinogens; Cricetinae; Electrocoagulation; Female; Hypothalamus; Injections, Intravenous; Iproniazid; Male; Mammary Neoplasms, Experimental; Methylthiouracil; Neoplasms, Experimental; Rats; Stereotaxic Techniques; Thyroid Neoplasms

Topics: Adenoma; Animals; Carcinoma; Carcinoma, Papillary; Cricetinae; Endoplasmic Reticulum; Golgi Apparatus; Methylthiouracil; Microscopy, Electron; Neoplasms, Experimental; Organoids; Thyroid Gland; Thyroid Neoplasms

Topics: Abnormalities, Drug-Induced; Aniline Compounds; Animals; Benz(a)Anthracenes; Carcinoma; Carcinoma, Squamous Cell; Female; Gestational Age; Hydrocephalus; Kidney Neoplasms; Maternal-Fetal Exchange; Methylthiouracil; Microcephaly; Neoplasms, Germ Cell and Embryonal; Nitroso Compounds; Pregnancy; Pregnancy, Animal; Rats; Thyroid Neoplasms; Urea; Urethane

Topics: Animals; Cytoplasmic Granules; DNA; Female; Male; Methylthiouracil; Precancerous Conditions; Rats; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Thyrotropin

Topics: Absorption; Animals; Methylthiouracil; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Thyroid Neoplasms; Transplantation, Homologous

Topics: Animals; Carcinogens; Iodine Isotopes; Methylthiouracil; Neoplasms, Experimental; Neoplasms, Radiation-Induced; Rats; Thyroid Neoplasms

Topics: Animals; Methylthiouracil; Neoplasm Transplantation; Neoplasms, Experimental; Rats; Thyroid Neoplasms

Topics: Adenoma; Animals; Carcinogens; Carcinoma; Fluorenes; Methylthiouracil; Neoplasm Metastasis; Neoplasms, Experimental; Propylthiouracil; Rats; Thiouracil; Thyroid Neoplasms

Topics: Adenoma; Carcinogens; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Pharmacology; Pituitary Neoplasms; Rats; Research; Thyroid Gland; Thyroid Neoplasms; Transplantation

Topics: Anesthesia; Anesthesia, Local; Anesthesia, Spinal; Antithyroid Agents; Barbiturates; Chloroform; Ether; Hyperthyroidism; Hypothermia, Induced; Iodine; Metabolism; Methylthiouracil; Refrigeration; Surgical Procedures, Operative; Thyroid Function Tests; Thyroid Neoplasms

Topics: Adenoma; Goiter; Graves Disease; Iodine; Methylthiouracil; Pathology; Pharmacology; Pituitary Gland; Rats; Research; Thyroid Neoplasms; Thyrotrophs; Triiodothyronine

Topics: Adrenal Gland Neoplasms; Adrenalectomy; Breast Neoplasms; Castration; Cortisone; Electrons; Endocrine Glands; Humans; Male; Methylthiouracil; Microscopy; Microscopy, Electron; Neoplasms; Neoplasms, Experimental; Ovarian Neoplasms; Pathology; Pituitary Gland; Pituitary Neoplasms; Prostatic Neoplasms; Rats; Research; Testicular Neoplasms; Thyroid Neoplasms; Thyroidectomy

Topics: Carcinogenesis; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Rats; Research; Thyroid Neoplasms; Triazoles

Topics: Adenoma; Goiter; Histology; Humans; Iodine; Methylthiouracil; Neoplasm Metastasis; Neoplasms; Pathology; Thyroid Neoplasms

Topics: Antithyroid Agents; Exophthalmos; Humans; Hyperthyroidism; Iodides; Iodine; Iodine Isotopes; Methylthiouracil; Perchlorates; Propylthiouracil; Radioisotopes; Radionuclide Imaging; Thyroid Neoplasms; Toxicology

Topics: Animals; Fluorenes; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Rats; Thiouracil; Thyroid Gland; Thyroid Neoplasms

Topics: Animals; Iodine; Iodine Radioisotopes; Methylthiouracil; Neoplasms; Neoplasms, Experimental; Thiouracil; Thyroid Gland; Thyroid Neoplasms