Multiwalled carbon nanotubes (MWCNT) induce DNA damage and cellular senescence in human peritoneal mesothelial LP9 cells

Multiwalled carbon nanotubes (MWCNTs) are nanomaterials with immense potential in many technological applications, such as in engineering, materials science, and medicine. Yet toxic and genotoxic effects of MWCNTs are still unclear. Notably, there is concern that certain MWCNTs may cause malignant mesothelioma, a cancer derived from mesothelial cells, particularly linked to asbestos exposure. We thus investigated the in vitro genotoxic activity of various tailor-made MWCNTs in primary human peritoneal mesothelial LP9 cells, under the auspices of a BMBF-funded project CarboTox (contract number: 03X0109A). LP9 cells were exposed for 24 h to 0.3-5.0 <ypsilon>H2AX, a well-known marker for DNA double-strand breaks. Consistent with cellular senescence, i.e. a state of irreversible terminal growth arrest resulting from cellular stress or DNA damage, we also observed increased expression of the gene encoding for P16INK4A, a tumor suppressor implicated in cell cycle arrest and cellular senescence. The impaired tubulin integrity noted after MWCNT exposure likely contributed also to cellular senescence induction. Altogether, our findings suggest marked genotoxic potential of long and straight MWCNTs leading to cellular senescence as a possible molecular mechanism in mesothelioma development after MWCNT exposure.