Inhibition of local and metastatic hepatoma growth and prolongation of survival after induction of hypothyroidism.

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.