Mutation spectrum in FE1-MUTA(TM) Mouse 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-Muta(TM) Mouse 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.
National Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen Ø, Denmark. nrj@nrcwe.dk
Nicklas Raun
NR
Jacobsen
Paul A
PA
White
John
J
Gingerich
Peter
P
Møller
Anne Thoustrup
AT
Saber
George R
GR
Douglas
Ulla
U
Vogel
Håkan
H
Wallin
D000818:Animals; D002460:Cell Line; D008168:Lung / Q000187:drug effects*; D051379:Mice; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects*; D053260:Soot / Q000633:toxicity*
D009153:Mutagens; D017382:Reactive Oxygen Species; D053260:Soot