Research Papers:

Low dose of Bisphenol A enhance the susceptibility of thyroid carcinoma stimulated by DHPN and iodine excess in F344 rats

Jing Zhang, Xiaochen Zhang, Yanan Li, Zhenzhen Zhou, Chuanlong Wu, Zhiyan Liu, Lanxiang Hao, Shanshan Fan, Fang Jiang, Yan Xie and Ling Jiang _

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Oncotarget. 2017; 8:69874-69887. https://doi.org/10.18632/oncotarget.19434

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Jing Zhang1,2,*, Xiaochen Zhang3,*, Yanan Li4, Zhenzhen Zhou5, Chuanlong Wu1, Zhiyan Liu6, Lanxiang Hao1,7, Shanshan Fan1, Fang Jiang1, Yan Xie1 and Ling Jiang1

1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan 250012, China

2Department of Hemodialysis, Heze Municipical Hospital, Heze 274000, China

3Department of Nursing, Heze Medical College, Heze 274000, China

4Department of Endocrinology, Laiwu City People’s Hospital, Laiwu 271100, China

5Department of Radiotherapy, Jinhua Municipal Central Hospital, Jinhua 321000, China

6Department of Pathology, Qilu Hospital of Shandong University, Jinan 250012, China

7Department of Endocrinology, Yancheng First People’s Hospital, Yancheng 224001, China

*These authors have contributed equally to this work

Correspondence to:

Ling Jiang, email: [email protected]

Keywords: Bisphenol A, iodine excess, thyroid carcinoma, estrogen receptor α, PCNA

Received: April 02, 2016     Accepted: June 02, 2017     Published: July 22, 2017


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.

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