PMID- 18044946 OWN - NLM STAT- MEDLINE DCOM- 20080312 LR - 20200930 IS - 1530-6984 (Print) IS - 1530-6984 (Linking) VI - 7 IP - 12 DP - 2007 Dec TI - DNA damage induced by multiwalled carbon nanotubes in mouse embryonic stem cells. PG - 3592-7 AB - Carbon nanotubes (CNTs) have shown promise as an important new class of multifunctional building blocks and innovative tools in a large variety of applications, ranging from nanocomposite materials through nanoelectronics to biomedical devices. Because of their unusual one-dimensional hollow nanostructure and unique physicochemical properties, CNTs are particularly useful as novel drug delivery tools and imaging agents. However, such biomedical applications will not be realized if there is no proper assessment of the potential hazards of CNTs to humans and other biological systems. Although a few reports on the cytotoxicity of CNTs have been published, very little is known about the toxicity at the molecular level, or genotoxicity, of CNTs in mammalian cells. We have for the first time assessed the DNA damage response to multiwalled carbon nanotubes (MWNTs) in mouse embryonic stem (ES) cells. We found that MWNTs can accumulate and induce apoptosis in mouse ES cells and activate the tumor suppressor protein p53 within 2 h of exposure. Furthermore, we also observed increased expression of two isoforms of base excision repair protein 8-oxoguanine-DNA glycosylase 1 (OGG1), double strand break repair protein Rad 51, phosphorylation of H2AX histone at serine 139, and SUMO modification of XRCC4 following the treatment with MWNTs. A mutagenesis study using an endogenous molecular marker, adenine phosphoribosyltransferase (Aprt), showed that MWNTs increased the mutation frequency by 2-fold compared with the spontaneous mutation frequency in mouse ES cells. These results suggest that careful scrutiny of the genotoxicity of nanomaterials is needed even for those materials, like multiwalled carbon nanotubes, that have been previously demonstrated to have limited or no toxicity at the cellular level. FAU - Zhu, Lin AU - Zhu L AD - Department of Biology, Department of Chemical and Materials Engineering, University of Dayton, Dayton, OH 45469, USA. FAU - Chang, Dong Wook AU - Chang DW FAU - Dai, Liming AU - Dai L FAU - Hong, Yiling AU - Hong Y LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20071129 PL - United States TA - Nano Lett JT - Nano letters JID - 101088070 RN - 7440-44-0 (Carbon) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Carbon/*toxicity MH - Cell Differentiation/drug effects MH - *DNA Damage MH - DNA Repair/drug effects MH - Embryo, Mammalian MH - Mice MH - Nanotubes/toxicity MH - Stem Cells/drug effects/*pathology/physiology EDAT- 2007/11/30 09:00 MHDA- 2008/03/13 09:00 CRDT- 2007/11/30 09:00 PHST- 2007/11/30 09:00 [pubmed] PHST- 2008/03/13 09:00 [medline] PHST- 2007/11/30 09:00 [entrez] AID - 10.1021/nl071303v [doi] PST - ppublish SO - Nano Lett. 2007 Dec;7(12):3592-7. doi: 10.1021/nl071303v. Epub 2007 Nov 29.