title: Cadmium Impairs p53 Activity in HepG2 Cells.
abstract: 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 p21(Cip1/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 p21(Cip1/WAF-1) expression and promote cell cycle progression and proliferation. The role of metallothioneins and possible conformational changes of p53 are discussed.
authors.affiliation: Department of Earth and Environmental Sciences, University of Milano Bicocca, piazza della Scienza 1, 20126 Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Urani
authors.affiliation: Department of Earth and Environmental Sciences, University of Milano Bicocca, piazza della Scienza 1, 20126 Milan, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Melchioretto
authors.affiliation: Institute for Health and Consumer Protection, Joint Research Centre, Via Enrico Fermi 2749, 21027 Ispra, Italy ; Dipartimento di Medicina Clinica e Sperimentale, Università dell'Insubria, 21100 Varese, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Fabbri
authors.affiliation: Institute for Health and Consumer Protection, Joint Research Centre, Via Enrico Fermi 2749, 21027 Ispra, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Bowe
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università dell'Insubria, 21100 Varese, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Maserati
authors.affiliation: Institute for Health and Consumer Protection, Joint Research Centre, Via Enrico Fermi 2749, 21027 Ispra, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gribaldo
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