%0 Journal Article
%T Cadmium Impairs p53 Activity in HepG2 Cells
%A C. Urani
%A P. Melchioretto
%A M. Fabbri
%A G. Bowe
%A E. Maserati
%A L. Gribaldo
%J ISRN Toxicology
%D 2014
%R 10.1155/2014/976428
%X 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. 1. Introduction Cadmium (Cd) is a toxic element present in air, soil, sediment, and water. It is released into the environment through the waste from heavy metal mining, manufactures of nickel-cadmium batteries, and from other industrial and agricultural activities. It is ubiquitously present in the environment and in food, thus leading to a potential risk of human exposure. Nonoccupational exposure is mainly from diet and smoking, due to an accumulation of Cd in tobacco plants [1]. More recently, Cd exposure has been associated with airborne particulate CdO and with Cd-containing quantum dots in medical therapy [2, 3]. Targets of Cd toxicity include liver, lung, kidney cortex, bone, the cardiovascular system, and the immune system ([4], see the reviews [5¨C7]). Cd and Cd compounds have been classified as human carcinogens (Group 1) by the World Health OrganizationĄ¯s International Agency for Research on Cancer [8] and by the National Toxicology Program [9]. Although Cd carcinogenicity has been recognized by epidemiological studies and animal experiments, the underlying mechanisms are still matter of research activities. Proposed mechanisms have been recently reviewed [10, 11] and range from thiol-containing protein affection and consequent production of reactive oxygen species, and interference with
%U http://www.hindawi.com/journals/isrn.toxicology/2014/976428/