Abstract
Thyroid carcinoma (TC) is the most common endocrine neoplasm. The risk of TC as a second primary malignancy (SPM) of breast cancer is significantly increased. Bisphenol A (BPA) is a widely contacted xenoestrogen and increases susceptibility to breast cancer through binding to estrogen receptor alpha (ERα). However, the effect of BPA on thyroid carcinogenesis has not been fully demonstrated. This present study aimed to characterize the effects of BPA on the development of TC using a Fischer 344 (F344) rat model. In this study, we established a TC model using female F344 rats pretreated with N-Bis (2-hydroxypropyl) nitrosamine (DHPN) at a single dose of 2800 mg/kg (the DA group) or without DHPN (the DN group), followed by stimulation with BPA at the level of 250 μg/kg (BPA250) or 1000 μg/kg (BPA1000) and a basic diet containing potassium iodine (KI, 1000 μg/L) for 64 weeks. We demonstrated that the incidence of TC in the BPA250 + KI of DA groups reached the highest at 50%, the incidence of thyroid hyperplasia lesions (including both tumors and focal hyperplasia lesions) in the BPA1000 + KI of DA groups reached 100% (P < 0.05). ERα protein and immunochemistry expression was upregulated in the BPA-exposed groups and the immunochemistry scores were positively correlated with PCNA. Thus, the present results indicate that BPA could enhance the susceptibility to TC stimulated by DHPN and iodine excess. ERα is probably involved in the proliferation effect of BPA. BPA or KI alone could not increase TC incidence.
Highlights
Thyroid carcinoma (TC) is the most common malignant tumor in the endocrine system and is mainly categorized into papillary, follicular, medullary, and anaplastic TC
To assess the iodine intake of rats, urinary iodine concentrations (UICs) in potassium iodine (KI) and the control of the DA groups were detected as 2 representative groups
TC models were developed using female Fischer 344 (F344) rats exposed to Bisphenol A (BPA) for 64 weeks with/without the basic treatment of KI and N-Bis nitrosamine (DHPN)
Summary
TC is the most common malignant tumor in the endocrine system and is mainly categorized into papillary, follicular, medullary, and anaplastic TC. Papillary thyroid carcinoma (PTC) accounts for more than 80% of all the pathological types [1]. The risk factors for the morbidity of TC include an excess and/or deficiency of iodine intake [2], radiation exposure [3], sex hormone, and environmental pollutants [4], among others. Tumorigenesis is due to the abnormality of gene alterations and regulations, which leads to unlimited cell proliferation [5]. Focal papillary hyperplasia and C-cell proliferation are common types of thyroid proliferative lesions [6, 7]. MUI: median of urinary iodine; UIC: urinary iodine concentration
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