Environmental Agents, Endocrine Disrupting Chemicals and Rat Thyroid Carcinogenesis

Abstract

Thyroid cell proliferation caused by environmental compounds is well known to be associated promotion of carcinogenesis. For example, kojic acid, a secondary fungal metabolite, induces cell proliferation in rat thyroid follicular epithelium, and promotes thyroid carcinogenesis after initiation with N-bis(2-hydroxypropyl)nitrosamine (DHPN). This was due to negative feedback through the pituitary-thyroid axis caused by inhibition of iodide uptake and iodine organification. Subcutaneous cholesterol pellets containing 17β-estradiol 3-benzoate also enhance rat thyroid carcinogenesis in ovariectomized female rats initiated with DHPN, although this was not the case with weak endocrine disrupting chemicals such as methoxychlor, atrazine and bisphenol A, which rather caused inhibition, possibly due to decrease in body weight gain. A high soybean diet enhances thyroid cell proliferation with increase in serum TSH level in synergism with a low iodine diet, presumably soybean diet primarily stimulate serum TSH release from the pituitary specifically under iodine deficiency conditions.