Evidence that ultrafine titanium dioxide induces micronuclei and apoptosis in Syrian hamster embryo fibroblasts.
Inhaled ultrafine titanium dioxide (UF-TiO2) particles cause pronounced pulmonary inflammation, in contrast to fine TiO2. Previous studies provide evidence for the production of reactive oxygen species by alveolar macrophages, after overloading with UF-TiO2 particles and cytotoxicity of UF-TiO2 in rat lung alveolar macrophages. UF-TiO2 also causes pulmonary fibrosis and lung tumors in rats. UF-TiO2 particles are photogenotoxic, but in general, information on the genotoxicity of UF-TiO2 is still limited. We studied the potential of UF-TiO2 (particle size less than or equal to 20 nm) and fine TiO2 (particle size > 200 nm) to induce chromosomal changes, which can be monitored by the formation of micronuclei (MN) in Syrian hamster embryo (SHE) cells. We also analyzed UF-TiO2-treated cells for apoptosis induction. The MN assay revealed a significant increase in MN induction (p less than or equal to 0.05) in SHE cells after treatment with UF-TiO2 (1.0 micro g/cm2) for 12 hr (mean, 24.5 MN/1,000 cells), 24 hr (mean, 31.13 MN/1,000 cells), 48 hr (mean, 30.8 MN/1,000 cells), 66 hr (mean, 31.2 MN/1,000 cells), and 72 hr (mean, 31.3 MN/1,000 cells). Bisbenzimide staining of the fixed cells revealed typical apoptotic structures (apoptotic bodies), and the apoptosis-specific "DNA ladder pattern" resulting from internucleosomal cleavage was identified by gel electrophoresis. Furthermore, transmission electron microscopy of the exposed cells revealed the typical chromatin compaction of apoptosis.
Rahman
Qamar
Q
Industrial Toxicology Research Centre, Division of Fibre Toxicology, Lucknow, India. qamar@avadh.net
Lohani
Mohtashim
M
Dopp
Elke
E
Pemsel
Heidemarie
H
Jonas
Ludwig
L
Weiss
Dieter G
DG
Schiffmann
Dietmar
D
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004396:Coloring Agents / Q000009:adverse effects*; D006224:Cricetinae; D004249:DNA Damage; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D008647:Mesocricetus / Q000196:embryology; D015162:Micronucleus Tests; D008854:Microscopy, Electron; D010316:Particle Size; D014025:Titanium / Q000009:adverse effects*
D004396:Coloring Agents; C009495:titanium dioxide; D014025:Titanium