Modifying Effects of Endocrine Disrupting Chemicals on N-bis(2-hydroxypropyl) Nitrosamine and Sulfadimethoxine-Induced Thyroid Carcinogenesis in Rats.

Abstract

To clarify whether 17β-estradiol 3-benzoate (EB), methoxychlor (MXC), atrazine (ATR), or bisphenol A (BPA) have any modifying effects on relatively late stages of thyroid carcinogenesis, six-week old female castrated F344 rats in Experiments 1 and 2 first received a single subcutaneous injection of 2000 mg/kg body wt of N-bis (2-hydroxypropyl) nitrosamine (DHPN) and, starting one week later, were given drinking water containing 1000 ppm sulfadimethoxine (SDM) for 8 weeks. Then, in Experiment 1, cholesterol pellets containing 0.5 mg EB were subcutaneously embedded and renewed every 4 weeks for 25 weeks. Controls received basal diet alone. In Experiment 2, rats of the control, MXC, ATR, or BPA group received diet containing no supplement, 1000 ppm MXC, 400 ppm ATR, and 10000 ppm BPA, respectively, for 27 weeks. Thyroid follicular cell hyperplasias, adenomas, and/or carcinomas were induced in all of the groups. In Experiment 1, the incidence of adenomas in the EB group was significantly increased, as compared to the corresponding control group value. In Experiment 2, the incidences of carcinomas in the MXC and BPA groups were significantly lower than in the corresponding control group. Serum estrogen levels and the PCNA labeling index for carcinomas in the EB group were significantly elevated but there was no clear alteration in serum thyroid related hormone levels. Serum T3 levels in the MXC and ATR groups were significantly reduced, whereas serum T4 was increased in these as well as the BPA group. No significant fluctuation in serum TSH levels was observed in these treated groups. The results of the present studies suggest that EB with strong estrogenic activity, but not MXC and BPA with only weak estrogenic activity or ATR, exerts promoting effects on thyroid carcinogenesis in rats.