Dados do Resumo

Título

The mixture of endocrine disruptors bisphenol A, nitrate, and perchlorate reduces the expression of differentiation markers and increases MAPK signaling pathway activity in thyrocytes.

Introdução

Bisphenol A, Nitrate, and Perchlorate are synthetic chemicals commonly found in drinking water. These substances are classified as endocrine disruptors because they interfere with the activity of endocrine glands and the function of various hormones in the body. Endocrine disruptors have already been correlated with an increased predisposition to and worse prognosis for several types of cancer. However, the relationship between thyroid carcinomas and exposure to a mixture of endocrine disruptors is not yet fully understood.

Objetivo

To evaluate the effect of exposure to a mixture of endocrine disruptors (BPA, Nitrate, and Perchlorate) on the expression and function of genes/proteins in thyrocytes.

Métodos

PCCl3 cells containing a vector of BRAFv600e mutation induction were treated or not (controls), for 48 hours to a mixture of endocrine disruptors (BPA, nitrate, and perchlorate) at concentrations of 10-7, 10-9, and 10-11 M. Gene and protein expression was assessed using qPCR and Western Blotting. . Activation of the MAPK and PKA signaling pathways was evaluated by Western Blotting.

Resultados

Exposure to the mixture of endocrine disruptors led to a decrease in the expression of genes involved in thyroid hormone biosynthesis, such as NIS, TG, TPO, and TSHR, in cells with doxycycline-induced BRAFv600e mutation. A reduction in NIS protein levels was also observed in cells exposed to the disruptor mixture. Furthermore, cells exposed to the disruptor mixture exhibited increased phosphorylation of ERK and CREB compared to the control group.

Conclusões

The hyperactivation of the MAPK signaling pathway has been correlated with reduced differentiation of thyrocytes into tumor cells. Our results suggest that the decreased expression of thyroid differentiation markers is associated with increased ERK activation in cells exposed to the mixture of endocrine disruptors, BPA, nitrate, and perchlorate. Our data indicate that exposure to the mixture of endocrine disruptors is detrimental to thyrocyte differentiation, potentially contributing to the development of thyroid tumors.

Financiador do resumo

Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES