title: Induction of apoptosis associated with chromosomal DNA fragmentation and caspase-3 activation in leukemia L1210 cells by TiO2 nanoparticles.
abstract: We investigated the effects of nanosized TiO2 particles on the death of mouse leukemia L1210 cells. TiO2 particles suppressed proliferation and induced cell death, as measured by lactate dehydrogenase (LDH) release into the culture medium. Chromatin condensation, which is typical of the initiation of cell death, was observed in approximately 14% cells cultured with titanium dioxide (TiO2) particles for 12 h. Furthermore, giant DNA fragments of approximately 2 Mbp and high-molecular-weight DNA fragments between 100 kbp and 1 Mbp were observed in cells cultured for 18 h with TiO2 particles. These giant and high-molecular-weight DNA fragments were further degraded into smaller DNA fragments, appearing as DNA ladders. Corresponding to the generation of DNA fragments, caspase-3 activity increased in cells treated with TiO2 particles. TiO2 particle-induced LDH release was not inhibited by cytochalasin D, an inhibitor of endocytosis. These results suggest that nanosized TiO2 particles can induce apoptosis associated with DNA fragmentation and caspase-3 activation and that TiO2 particle-induced apoptosis is not caused by endocytosis but is associated with contact of the particles with the cell surface.
authors.affiliation: Division of Biological Measurement and Applications, Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 920-1192, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Takaki
authors.affiliation: Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Hashii
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, Kobe 657-8501, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ogino
authors.affiliation: Division of Biological Measurement and Applications, Institute of Nature and Environmental Technology, Kanazawa University, Kanazawa 920-1192, Japan. Electronic address: nshimizu@t.kanazawa-u.ac.jp.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000633:toxicity; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects*; D004789:Enzyme Activation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D053768:Metal Nanoparticles / Q000633:toxicity*; D051379:Mice; D014025:Titanium / Q000633:toxicity
chemical_list: D001672:Biocompatible Materials; C009495:titanium dioxide; D015638:Cytochalasin D; D014025:Titanium; D007770:L-Lactate Dehydrogenase; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Caspase-3; DNA fragmentation; Endocytosis; Nanoparticles; Titanium dioxide