Table of Contents
ISRN Toxicology
Volume 2014, Article ID 976428, 9 pages
Research Article

Cadmium Impairs p53 Activity in HepG2 Cells

1Department of Earth and Environmental Sciences, University of Milano Bicocca, piazza della Scienza 1, 20126 Milan, Italy
2Institute for Health and Consumer Protection, Joint Research Centre, Via Enrico Fermi 2749, 21027 Ispra, Italy
3Dipartimento di Medicina Clinica e Sperimentale, Università dell’Insubria, 21100 Varese, Italy

Received 20 November 2013; Accepted 15 January 2014; Published 13 March 2014

Academic Editors: P. S. Rajini and F. Remiao

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.


Cadmium and cadmium compounds are contaminants of the environment, food, and drinking water 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 cadmium outcomes at cell and molecular level. The present work is designed to gain an insight into the mechanism of 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 , 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 expression and promote cell cycle progression and proliferation. The role of metallothioneins and possible conformational changes of p53 are discussed.