propylthiouracil and Neoplasm-Metastasis

The injection of a retrovirus carrying the v-ras-Ki oncogene into the thyroid gland of adult Fischer rats induces thyroid carcinomas when associated with a treatment of the animals with a goitrogenic agent. More than one hundred adult Fischer rats have been treated with the goitrogen agent propylthiouracil in order to induce thyroid hyperplasia. Twenty days after treatment, rat thyroid glands, surgically prepared, were injected with the Kirsten murine sarcoma virus (KiMSV). Within three months more than 90% of the animals developed thyroid tumors. Histologically the tumors had the appearance of well differentiated carcinomas. Thirty animals had lung metastases in addition to the thyroid carcinoma. The presence of KiMSV specific transcripts and the specific transforming protein (p21) in thyroid carcinomas and in the metastases was detected by Northern blot analysis and immunoprecipitation, respectively. Only three rats, among thirty that had not received the goitrogen treatment, but only the injection with KiMSV, developed thyroid carcinomas of very small size and with a very long latency period (almost one year). The results described represent the first instance of thyroid carcinoma induction by retroviruses. This system may be regarded as a useful model to investigate the process of thyroid carcinogenesis in vivo. These results suggest that this model may also be useful for investigating the interaction between hormones and cells harboring the activated oncogene in the development of thyroid carcinoma since activated ras oncogenes have been implicated in human thyroid carcinoma.

Topics: Animals; Carcinoma; Disease Models, Animal; Genes, ras; Kirsten murine sarcoma virus; Neoplasm Metastasis; Oncogene Protein p21(ras); Oncogene Proteins, Viral; Propylthiouracil; Rats; Rats, Inbred F344; Sarcoma Viruses, Murine; Thyroid Neoplasms; Thyrotropin

The local growth rate of Morris Hepatoma 44 (generation time, 6 months) was inhibited by 66 to 87%, and host survival was prolonged by 36 to 78% after the induction of hypothyroidism within 2 weeks of tumor implantation by propylthiouracil (0.1% in Purina chow), 131I(1 mCi/100 g body weight i.p.), or surgical thyroidectomy. In additional experiments, we studied the effects of inducing hypothyroidism (131I) at different stages in the natural history of Morris Hepatoma 44 on local and metastatic growth as well as on host survival. Induction of hypothyroidism within 2 weeks of tumor implantation (Group I) reduced local tumor growth as well as the number and size of pulmonary metastases, and prolonged survival by 70 to 80%. Induction of hypothyroidism at 6 weeks postimplantation when tumors were palpable (Group II) inhibited local growth by 39%, reduced the number and size of pulmonary metastases by approximately 80%, and prolonged host survival by 35%. Initiation of 131I treatment at 11 weeks when microscopic pulmonary emboli were present in most animals (Group III) reduced local growth by 19% and the number and size of pulmonary metastases by 72 and 50%, respectively. In this case, survival was prolonged by 17%. We conclude from these results that the local and metastatic growth of Morris hepatoma 44 as well as host survival are thyroid hormone-dependent processes. The mechanisms responsible for these observations remain to be explained.

Topics: Animals; Hypothyroidism; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Neoplasm Metastasis; Propylthiouracil; Rats; Thyroidectomy

The influence of some stress agents applied during variable periods of time and under various modifications of the endocrine status was studied on the lymphotropic metastases of the 256 Walker carcinosarcoma, grafted intratesticulary in rats. Different reactivity of metastases, when compared to that of primary tumors was found in relation to the action of some compounds influencing the hormonal balance. Stress enhances the primary tumor development, while the metastatic growth is inhibited. However later on, sudden enhancement of the metastasis growth was observed. Adrenalectomy, as well as testosterone, thyroxine, of Stilbostat administration inhibit the metastasis, whereas cortisone, or antithyroid drug administration enhance the metastasis. The in vitro study of the tumor cell proliferation suggests some immunemorphological involvements in the development of this process.

Topics: Adrenalectomy; Animals; Carcinoma 256, Walker; Cell Division; Cortisone; Diethylstilbestrol; Male; Neoplasm Metastasis; Propylthiouracil; Rats; Stress, Physiological; Testosterone; Thyroxine

Topics: Adenocarcinoma; Aged; Autoradiography; Female; Humans; Hyperthyroidism; Iodine Radioisotopes; Ion Exchange Resins; Neoplasm Metastasis; Propylthiouracil; Radionuclide Imaging; Thyroid Neoplasms; Triiodothyronine

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Female; Hypothyroidism; Liver Neoplasms; Neoplasm Metastasis; Neoplasms, Experimental; Propylthiouracil; Rats; Thyroid Gland; Thyroidectomy; Thyrotropin; Thyroxine; Triiodothyronine

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

Topics: Adenocarcinoma; Adolescent; Humans; Infertility; Iodine Isotopes; Lymphatic Metastasis; Neck Dissection; Neoplasm Metastasis; Neoplasms; Pathology; Propylthiouracil; Radiation Injuries; Surgical Procedures, Operative; Thyroid Function Tests; Thyroid Hormones; Thyroid Neoplasms; Thyroidectomy; Toxicology