Effects of Iodine Deficiency and High-Fat Diet on N-Nitrosomethylurea induced Mammary Cancers in Rats1

The effects of an altered content of dietary iodine and fat on the development of N-nitrosomethylurea-induced mam many tumors in rats were studied and correlated with thyroid and pituitary function studies. In three separate experiments, animals fed a semisynthetic diet containing 11.8% fat had an earlier time of tumor appearance and greater tumor burden than did controls maintained on a diet containing 4.6% fat. These diet-associated changes were markedly inhibited by ovaniectomy, indicating that the tumor growth was hormone responsive. We examined the possibility thatthedietwithincreasedfatcontentenhanced tumor growth through alterations in prolactin metabolism but could find no consistent elevation in serum probactin and no increase in pituitary prolactin synthesis in vitro. Our data further showed that rats on an iodine-deficient form of the high-fat diet had no greater tumor growth than did animals receiving an iodine-supplemented form of the same diet. We conclude from these results that iodine deficiency does not promote mammary tumorigenesis. An incidental finding of great interest was that ovariec tomy led to a highly significant depression of thyroid-stim ulating hormone production in vitro. This suggests that estrogens may directly influence thyroid-stimulating hor mone synthesis in vivo and thus contribute to the sex related differences in thyroid physiology.