Abstract
Synthetic metal oxide nanomaterials exert toxicity via two general mechanisms: Release of free ions at concentrations which exert toxic effects upon the target cell, or specific surface-mediated physicochemical processes leading to the formation of hydroxyl free radicals and other reactive oxygen species which act to disrupt cell membranes and organelles. From a regulatory standpoint this presents a potential problem since it is not trivial to detect free metal ions in the presence of nanoparticles in biological or natural media. This makes efforts to identify the route of uptake difficult. Although in vitro studies of zinc oxide nanoparticles suggest that toxicity to the soil bacterium Cupriavidus necator is exerted in a similar manner to zinc acetate, we found no free Zn ion is associated with nanoparticle suspensions. The proteome of cells subjected to equal concentrations of either the nanoparticle or zinc acetate suggest that the mode of toxicity is quite different for the two forms of Zn, with a number of membrane-associated proteins up-expressed in response to nanoparticle exposure. Our data suggests that nanoparticles act to interrupt cell membranes thereby causing cell death rather than exerting a strictly toxic effect. We also identify potentially useful genes to serve as biomarkers of membrane disruption in toxicogenomic studies with nanoparticles or to engineer biosensor organisms.
Acknowledgements
The authors are grateful to Keith Goulding and an anonymous reviewer for helpful criticism of the original manuscript. Any opinions, findings, conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the EPA. This work has not been subjected to EPA review and no official endorsement should be inferred.
Declaration of interest: Rothamsted Research receives grant-aided support from the Biotechnology and Biological Sciences Research Council of the UK. Major funding was provided by the U.S. Environmental Protection Agency's (EPA) Science to Achieve Results (STAR) Grant No. RD832530. Partial support was also provided by EPA STAR grant RD834574 and by the Natural Environment Research Council of the UK through grant NE/H013679/1. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.