Mutation spectrum in FE1-MUTA(TM) Mouse lung epithelial cells exposed to nanoparticulate carbon black

TY - JOUR

T1 - Mutation spectrum in FE1-MUTA(TM) Mouse lung epithelial cells exposed to nanoparticulate carbon black

AU - Jacobsen, Nicklas Raun

AU - White, Paul A

AU - Gingerich, John

AU - Møller, Peter

AU - Saber, Anne Thoustrup

AU - Douglas, George R

AU - Vogel, Ulla

AU - Wallin, Håkan

N1 - 2010 Wiley-Liss, Inc.

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

AB - 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.

U2 - 10.1002/em.20629

DO - 10.1002/em.20629

M3 - Journal article

C2 - 20963790

SN - 0893-6692

VL - 52

SP - 331

EP - 337

JO - Environmental and Molecular Mutagenesis

JF - Environmental and Molecular Mutagenesis

IS - 4

ER -