Wei, Ying, Shen, Hongkuan, Gao, Changsheng, Du, Yuan, Zhao, Yanli, Wang, Yuhang, Zhou, Shi, Li, Jinlian, Zhao, Baojiang, and Wu, Dongmei
Some heavy metals in the environment may have estrogen-like activity, which probably lead to major diseases such as breast cancer. It is of great importance to establish new methods to evaluate the estrogen effect of heavy metals from multiple angles due to the complex mechanism of estrogen effect. In this paper, using MCF-7 cells as model, the electrochemical detection mechanism of the estrogen effect of heavy metal cadmium (Cd) was studied. The two electrochemical signals of MCF-7 cells derived from uric acid (0.30 V) and the mixture of guanine and xanthine (0.68 V) increased in a time and dose-dependent manner when MCF-7 cells induced by Cd, reaching the maximum at 96 h and 10−9 mol L−1. Further studies found that three purine metabolism pathways about de novo synthesis, salvage synthesis and decomposition metabolism were activated by the estrogen effect of Cd. The expression of PRPP amidotransferase in purine de novo synthesis pathway and HPRT in purine salvage synthesis pathway up-regulated, especially HPRT, which promoted cell proliferation together. Nevertheless, the expression of GDA and ADA, the key enzymes in purine decomposition metabolism pathway, up-regulated in a time and dose-dependent manner, which had same tendency with that of ERα, thereby increased the content of intracellular hypoxanthine, guanine, xanthine and uric acid, and enhanced electrochemical signals. [Display omitted] • Cd induced purine de novo and salvage synthesis, especially salvage synthesis. • Both purine de novo and salvage synthesis provided energy for cell proliferation. • Purine catabolism was induced by Cd in a time-dependent manner. • Purine metabolism induced by Cd enhanced electrochemical signals. [ABSTRACT FROM AUTHOR]