期刊
NANOTOXICOLOGY
卷 9, 期 2, 页码 138-147出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/17435390.2014.900582
关键词
Mechanistic toxicology; nanotoxicology; risk assessment
资金
- Universitat Autonoma de Barcelona (UAB)
- UAB PIF fellowships
- Generalitat de Catalunya [2009SGR-725]
- UAB [APOSTA-2011]
- Spanish Ministry of Education and Science [SAF2011-23146]
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 mg/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.
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