DNA double strand breaks (DNA DSBs) are a very rapid response to DNA damage that occurs in cells subjected to radiation, exposure to toxic substances, and other environmental stresses. The inability to repair these breaks can lead to carcinogenesis. One of the earliest responses to DNA DSBs is the phosphorylation of a histone, H2AX, at serine 139, yielding a focal product (-H2AX) that can be detected by a fluorescent antibody. A study was undertaken to compare the induction of DNA DSBs in normal (SAE) and cancer cells (A549) after exposure to asbestos (crocidolite), a proven carcinogen, silica a suspected carcinogen, and titanium dioxide (an inert particle, recently reported to be carcinogenic in animals). The results indicate that crocidolite induced greater DNA DSBs than silica and TiO2 regardless of cell type. DNA DSBs due to crocidolite were higher in normal cells than in cancer cells. Silica and TiO2 induced higher DNA DSBs in cancer cells than in normal cells. The production of reactive oxygen species (ROS) was found to be highest in cells exposed to crocidolite followed in potency by silica and TiO2. The generation of ROS was higher in normal cells than in cancer cells. Cell viability assay indicated that crocidolite caused the greatest cytotoxicity in both cell types. Apoptosis, measured by caspase 3/7 activity, was highest in crocidolite-exposed cells followed in potency by TiO2 and silica. The results of this study indicate that crocidolite has a greater carcinogenic potential than silica and TiO2 judged by its ability to cause sustained genomic instability in normal lung cells.