Mutation spectrum in FE1‐MUTATMMouse lung epithelial cells exposed to nanoparticulate carbon black

It has been shown previously that carbon black (CB), Printex 90 exposure induces cII and lacZ mutants in the FE1‐MutaTMMouse lung epithelial cell line and causes oxidatively damaged DNA and the production of reactive oxygen species (ROS). The purpose of this study was to determine the mutation spectrum in the cII gene of Printex 90 exposed cells. Cells exposed to CB have a substantially different mutation spectrum in the cII gene compared with vehicle exposed controls. The mutation spectra differ both in the positions (P < 0.0001) and types of the mutations (P < 0.0001). Exposure to Printex 90 increased the number of single base deletions by 2.3‐fold and larger deletions by 1.9‐fold. Most single base deletions were within two repetitive sequences in cII, but the large deletions were not. The mechanism behind the large deletions is not yet known. The largest increases in base substitutions were observed in G:C→T:A, G:C→C:G, and A:T→T:A transversion mutations; this is in keeping with a genetic finger print of ROS and is further substantiated by the observations that Printex 90 generates ROS and oxidatively damaged DNA. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.

[1]  H. Sugiyama,et al.  Possible cause of G-C-->C-G transversion mutation by guanine oxidation product, imidazolone. , 2001, Chemistry & biology.

[2]  S. Tannenbaum,et al.  Oxidation of 7,8-dihydro-8-oxoguanine affords lesions that are potent sources of replication errors in vivo. , 2002, Biochemistry.

[3]  P. White,et al.  Development and characterization of a stable epithelial cell line from Muta™Mouse lung , 2003, Environmental and molecular mutagenesis.

[4]  Slobodan V. Jovanovic,et al.  How Easily Oxidizable Is DNA? One-Electron Reduction Potentials of Adenosine and Guanosine Radicals in Aqueous Solution , 1997 .

[5]  Roel P F Schins,et al.  Inhaled particles and lung cancer. Part A: Mechanisms , 2004, International journal of cancer.

[6]  U. Vogel,et al.  Diesel exhaust particles are mutagenic in FE1-MutaMouse lung epithelial cells. , 2008, Mutation research.

[7]  D. Court,et al.  The phage λ CII transcriptional activator carries a C-terminal domain signaling for rapid proteolysis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[8]  T R Skopek,et al.  Statistical test for the comparison of samples from mutational spectra. , 1987, Journal of molecular biology.

[9]  A. Grollman,et al.  Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG , 1991, Nature.

[10]  W. T. Adams,et al.  Computer program for the analysis of mutational spectra: application to p53 mutations. , 1994, Carcinogenesis.

[11]  U. Vogel,et al.  A strong genotoxic effect in mouse skin of a single painting of coal tar in hairless mice and in MutaMouse. , 2000, Mutation research.

[12]  U. Vogel,et al.  Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation , 2005, Archives of Toxicology.

[13]  J. Abel,et al.  Distinct spectrum of mutations induced by crocidolite asbestos: clue for 8-hydroxydeoxyguanosine-dependent mutagenesis in vivo. , 2002, Cancer research.

[14]  T. Hei,et al.  New Insight into Intrachromosomal Deletions Induced by Chrysotile in the gpt delta Transgenic Mutation Assay , 2006, Environmental health perspectives.

[15]  U. Vogel,et al.  Pharmacological coal tar induces G:C to T:A transversion mutations in the skin of muta mouse. , 2001, Pharmacology & toxicology.

[16]  H. Takano,et al.  Mutations in the lungs of gpt delta transgenic mice following inhalation of diesel exhaust , 2007, Environmental and molecular mutagenesis.

[17]  D. Court,et al.  The phage lambda CII transcriptional activator carries a C-terminal domain signaling for rapid proteolysis. , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Adams Wt,et al.  Statistical test for the comparison of samples from mutational spectra , 1987 .

[19]  Antonio Marcomini,et al.  Genotoxicity, cytotoxicity, and reactive oxygen species induced by single‐walled carbon nanotubes and C60 fullerenes in the FE1‐Muta™Mouse lung epithelial cells , 2008, Environmental and molecular mutagenesis.

[20]  J. Heddle.  On clonal expansion and its effects on mutant frequencies, mutation spectra and statistics for somatic mutations in vivo. , 1999, Mutagenesis.

[21]  K Fujikawa,et al.  [Oxidative DNA damage]. , 2001, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[22]  J. Cadet,et al.  Oxidative damage to DNA: formation, measurement and biochemical features. , 2003, Mutation research.

[23]  Nicklas Raun Jacobsen,et al.  Increased mutant frequency by carbon black, but not quartz, in the lacZ and cII transgenes of muta™mouse lung epithelial cells , 2007, Environmental and molecular mutagenesis.

[24]  N. Jacobsen,et al.  Role of oxidative damage in toxicity of particulates , 2010, Free radical research.

[25]  M. Evans,et al.  Oxidative DNA damage and disease: induction, repair and significance. , 2004, Mutation research.

[26]  A. Zuckerman,et al.  IARC Monographs on the Evaluation of Carcinogenic Risks to Humans , 1995, IARC monographs on the evaluation of carcinogenic risks to humans.

[27]  P. Harbach,et al.  Spontaneous mutation spectrum at the lambda cII locus in liver, lung, and spleen tissue of Big Blue® transgenic mice , 1999, Environmental and molecular mutagenesis.

[28]  B. Epe,et al.  Oxidative DNA damage and mutations induced by a polar photosensitizer, Ro19-8022. , 1999, Mutation research.

[29]  H. Kamiya.  Mutagenicities of 8-hydroxyguanine and 2-hydroxyadenine produced by reactive oxygen species. , 2004, Biological & pharmaceutical bulletin.

[30]  G. Pfeifer,et al.  Mutagenesis induced by the nitric oxide donor sodium nitroprusside in mouse cells. , 2006, Mutagenesis.

[31]  A. Kohara,et al.  Mutation spectrum of o-aminoazotoluene in the cII gene of lambda/lacZ transgenic mice (MutaMouse). , 2001, Mutation research.

[32]  Günter Oberdörster,et al.  Formation of PAH-DNA adducts after in vivo and vitro exposure of rats and lung cells to different commercial carbon blacks. , 2005, Toxicology and applied pharmacology.