The particulate phase of diesel engine exhaust is likely carcinogenic. However, the mechanisms of diesel exhaust particles (DEPs) induced mutagenicity/carcinogenicity are still largely unknown. We determined the mutant frequency following eight repeated 72 h incubations with 37.5 or 75 mu g/ml DEP (NIST SRM 1650) in the FE1-Muta(TM)Mouse lung epithelial cell line. We measured DEP-induced acellular and intracellular production of reactive oxygen species (ROS) and compared with ROS production induced by carbon black, which WE, have previously shown is mutagenic in this cell line [N.R. Jacobsen, A.T. Saber, P. White, P. Moller, G. Pojana, U. Vogel, S. Loft, J.Gingerich, L. Soper, G.R. Douglas, H. Wallin. Increased mutant frequency by carbon black,, but not quartz, in the lacZ and cII transgenes of muta(TM)mouse lung epithelial cells, Environ. Mol. Mutagen. 48(6) (2007) 451-461]. The mutant frequency was marginally elevated in cells treated with 37.5 mu g/ml DEP (1.29-fold [95% CI: 0.96-1.601, p = 0.08) and significantly increased in cells treated with 75 mu g/ml DEP (1.55-fold [95% CI: 1.23-1.871, p <0.001). ROS production from DEP was low both within cells and in acellular systems when compared to carbon black. These results show that DEP are mutagenic in a mammalian cell line in vitro and that additional pathways besides ROS production, such as those involving the presence of polycyclic aromatic hydrocarbons, likely are involved in the mutagenesis. (C) 2008 Elsevier B.V. All rights reserved.