Research Article Cadmium Impairs p53 Activity in HepG2 Cells

Copyright © 2014 C. Urani et al.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cadmiumand cadmiumcompounds are contaminants of the environment, food, anddrinkingwater and are important constituents of cigarette smoke. Cd exposure has also been associated with airborne particulate CdO and with Cd-containing quantum dots in medical therapy. Adverse cadmium effects reported in the literature have stimulated during recent years an ongoing discussion to better elucidate cadmiumoutcomes at cell andmolecular level.Thepresentwork is designed to gain an insight into themechanismof p53 impairment at gene and protein level to understand Cd-induced resistance to apoptosis. We used a hepatoma cell line (HepG2) derived from liver, known to be metal responsive. At genotoxic cadmium concentrations no cell cycle arrest was observed. The p53 at gene and protein level was not regulated. Fluorescence images showed that p53 was correctly translocated into the nucleus but that the p21Cip1/WAF-1, a downstream protein of p53 network involved in cell cycle regulation, was not activated at the highest cadmium concentrations used. The miRNAs analysis revealed an upregulation of mir-372, an miRNA able to affect p21Cip1/WAF-1 expression and promote cell cycle progression and proliferation.The role of metallothioneins and possible conformational changes of p53 are discussed. 1