Comparing the genotoxicity of a multiwalled carbon nanotube and crocidolite towards the evaluation of its potential impact on the workers’ health

Ventura, Célia; Sousa Uva, António; Silva, Maria João

http://hdl.handle.net/10400.18/5038

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Authors

Ventura, Célia

Sousa Uva, António

Silva, Maria João

Abstract(s)

Background: Multiwalled carbon nanotubes (MWCNT) are one of the most promising and widespread class of manufactured nanomaterials, with several industrial and biomedical applications. However, their unique physicochemical properties may have detrimental effects on human health upon unintentional exposure by inhalation. Although there is still no sufficient epidemiological and toxicological data on most MWCNT, several professional and scientific organizations adopted a precautionary principle and considered MWCNT as an occupational hazard. In vitro toxicological studies can contribute to fulfil the gaps on the knowledge about their potential health adverse effects and to identify biomarkers for human biomonitoring, particularly in the workplace. Aim- This study was aimed at characterizing the cytotoxic and genotoxic effects of NRCWE-006, a high aspect-ratio rigid MWCNT, comparatively to crocidolite, a well-known tumorigenic asbestos fiber causing mesothelioma, using a co-culture of alveolar epithelial cells (A549) and monocyte-derived macrophages (THP-1). Methods – The MTT, the comet and the micronucleus assays were performed on a co-culture of A549 and differentiated THP-1 cells following exposure to a concentration- range of NRCWE-006 or crocidolite. Results- Both NRCWE-006 and crocidolite revealed cytotoxicity by the MTT assay. NRCWE-006 did not induce a detectable level of DNA breaks under the comet assay conditions tested, while a significant increase in the micronucleus frequency was detected at 6.25 and 12.5 µg/cm2. In contrast, crocidolite revealed a clear dose-dependent increase in the level of DNA strand breaks (comet assay) and induced a significant increase in the micronucleus frequency at the highest concentrations tested (10 and 20 µg/cm2). Discussion and Conclusions – Our results suggest that NRCWE-006 is less cytotoxic than crocidolite to alveolar cells grown in co-culture with monocyte-derived macrophages. As expected, crocidolite was clearly genotoxic, given that it was able to induce DNA and chromosome damage, probably due to its known potential of ROS production. On the other hand, even though NRCWE-006 did not cause DNA damage, it demonstrated aneugenic/clastogenic effects at the two lowest concentrations, which are closer to the ones that may represent a concern in terms of occupational exposure.