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Human pleural mesothelial MeT-5A cells are a limited in vitro model for detection of potential asbestos-like genotoxic effects of multiwall carbon nanotubes

: Ziemann, Christina; Reamon-Büttner, Stella Marie; Hackbarth, Anja; Brockmeyer, Heidrun; Rahmer, Hartmut; Bellmann, Bernd

The Toxicologist 52 (2013), No.1, pp.92, Abstract PS 434
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <52, 2013, San Antonio/Tex.>
Journal Article, Conference Paper
Fraunhofer ITEM ()

Multiwall carbon nanotubes (MWCNT) are nanomaterials with important technological impact. But, depending on diameter and length some MWCNT may induce fiber-like toxicity/genotoxicity, similar to asbestos. Thus, a project funded by SOT 2013 ANNUAL MEETING 93 the German Federal Ministry of Education and Research (contract No. 03X0109A) focuses on potential adverse biological effects and toxicity determining characteristics of divers MWCNT, both in vivo and in vitro, using long fiber amosite asbestos (LFA) as positive control. Since mesothelial cells are targets for adverse effects of asbestos, notably mesothelioma development, human SV40-transformed, non-malignant pleural mesothelial MeT-5A cells were initially chosen as in vitro model. In this study part, their usefulness for investigation of potential asbestos-like adverse effects of MWCNT in vitro was characterized. Proliferation parameters and a MWCNT-optimized lactate dehydrogenase assay indicated concentration-dependent cytotoxicity of LFA (2, 10 and 20 g/cm2) in MeT-5A cells. LFA also induced DNA-strand breaks and oxidative DNA-damage in the hOGG1-modified comet assay. For determination of MWCNT-related aneugenic effects/spindle fiber damage, basal frequency of micronuclei, chromosome aberrations, and altered meta-, ana- and telophase morphology was firstly determined. MeT-5A cells exhibited highly variable chromosome numbers (6.5% cells with normal 46 chromosomes), a markedly higher spontaneous micronucleus frequency, compared to rodent bone marrow erythrocytes (~15-fold) and V79 cells ~5-fold), and a high frequency of aberrant mitosis stages (bridges, lagging chromosomes, multipolar divisions). In conclusion, MeT-5A cells are a limited in vitro model to study potential asbestoslike effects of MWCNT. Cells are responsive to asbestos, but demonstrate marked genomic instability and thus limited significance concerning genotoxic effects. LP9 and LP9/TERT-1 cells are thus currently characterized as alternative models.