Cytotoxic effects of Cerium Dioxide nanoparticles in primary human cells are mediated through apoptosis and autophagy

Wednesday, October 10, 2012 — Poster Session II
Noon – 2:00 p.m	Natcher Conference Center, Building 45	NIEHS	CELLBIO-3

Authors

• S. Hussain
• A.B. Rice
• J.D. Marshburn
• N.J. Walker
• S. Garantziotis

Abstract

Cerium dioxide nanoparticles (CeO2 NPs) are used commercially, e.g. as diesel fuel additive, and novel therapeutic applications are actively being pursued. We investigated the cytotoxic effects of CeO2 NPs in primary human cells (monocytes, bronchial epithelial cells and alveolar macrophages) at pharmacologically relevant doses. CeO2 NPs and their suspensions were thoroughly characterized, including using transmission electron microscopy (TEM), dynamic light scattering (DLS), and zeta potential analysis. Cells were exposed to NPs (0.5-10 µg/mL) for 20 or 40 hours and mechanisms of cell injury were studied. TEM revealed that NPs are internalized by cells and are found either in vesicles or free in the cytoplasm. NP exposure leads to decrease in cell viability. CeO2-treated cells exhibit activation of Bax, loss of mitochondrial membrane potential and DNA fragmentation. NP toxicity is caused by mitochondrial damage leading to apoptosis inducing factor (AIF) release, but not due to caspase activation or reactive oxygen species production. Moreover, NP exposure leads to autophagy, which is further increased after pharmacological inhibition of p53. Inhibition of autophagy partially reverses cell death by NPs. We demonstrate that apoptosis and autophagy acts in a coordinated fashion to cause cytotoxicity after CeO2 NP exposure.

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