Long-term exposures to low doses of cobalt nanoparticles induce cell transformation enhanced by oxidative damage. Issue 2 (8th April 2014)

• Record Type: Journal Article
• Authors: Annangi, Balasubramanyam; Bach, Jordi; Vales, Gerard; Rubio, Laura; Marcos, Ricard; Hernández, Alba
• Is Part Of: Nanotoxicology. Volume 9:Issue 2(2015:Mar.)
• Page Start: 138
• Page End: 147
• Publication Date: 2014-04-08
• Subjects: Mechanistic toxicology -- nanotoxicology -- risk assessment; Toxicology -- Periodicals; 615.9
• DOI: 10.3109/17435390.2014.900582
• Languages: English
• ISSNs: 1743-5390

Abstract

Abstract: A weak aspect of the in vitro studies devoted to get information on the toxic, genotoxic and carcinogenic properties of nanomaterials is that they are usually conducted under acute-exposure and high-dose conditions. This makes difficult to extrapolate the results to human beings. To overcome this point, we have evaluated the cell transforming ability of cobalt nanoparticles (CoNPs) after long-term exposures (12 weeks) to sub-toxic doses (0.05 and 0.1 µg/mL). To get further information on whether CoNPs-induced oxidative DNA damage is relevant for CoNPs carcinogenesis, the cell lines selected for the study were the wild-type mouse embryonic fibroblast (MEF Ogg1 +/+ ) and its isogenic Ogg1 knockout partner (MEF Ogg1 − / − ), unable to properly eliminate the 8-OH-dG lesions from DNA. Our initial short-term exposure experiments demonstrate that low doses of CoNPs are able to induce reactive oxygen species (ROS) and that MEF Ogg1 − / − cells are more sensitive to CoNPs-induced acute toxicity and oxidative DNA damage. On the other hand, long-term exposures of MEF cells to sub-toxic doses of CoNPs were able to induce cell transformation, as indicated by the observed morphological cell changes, significant increases in the secretion of metalloproteinases (MMPs) and anchorage-independent cell growth ability, all cancer-like phenotypic hallmarks. Interestingly, such changes were significantly dependent on the cell line used, the Ogg1 − / − cells being particularly sensitive. Altogether, the data presented here confirms the potential carcinogenic risk of CoNPs and points out the relevance of ROS and Ogg1 genetic background on CoNPs-associated effects.