title: Comparative study of toxic effects of anatase and rutile type nanosized titanium dioxide particles in vivo and in vitro.
abstract: Two types of nanosized titanium dioxide, anatase (anTiO2) and rutile (rnTiO2), are widely used in industry, commercial products and biosystems. TiO2 has been evaluated as a Group 2B carcinogen. Previous reports indicated that anTiO2 is less toxic than rnTiO2, however, under ultraviolet irradiation anTiO2 is more toxic than rnTiO2 in vitro because of differences in their crystal structures. In the present study, we compared the in vivo and in vitro toxic effects induced by anTiO2 and rnTiO2. Female SD rats were treated with 500 ?g/ml of anTiO2 or rnTiO2 suspensions by intra-pulmonary spraying 8 times over a two week period. In the lung, treatment with anTiO2 or rnTiO2 increased alveolar macrophage numbers and levels of 8-hydroxydeoxyguanosine (8-OHdG); these increases tended to be lower in the anTiO2 treated group compared to the rnTiO2 treated group. Expression of MIP1??mRNA and protein in lung tissues treated with anTiO2 and rnTiO2 was also significantly up-regulated, with MIP1??mRNA and protein expression significantly lower in the anTiO2 group than in the rnTiO2 group. In cell culture of primary alveolar macrophages (PAM) treated with anTiO2 and rnTiO2, expression of MIP1??mRNA in the PAM and protein in the culture media was significantly higher than in control cultures. Similarly to the in vivo results, MIP1??mRNA and protein expression was significantly lower in the anTiO2 treated cultures compared to the rnTiO2 treated cultures. Furthermore, conditioned cell culture media from PAM cultures treated with anTiO2 had less effect on A549 cell proliferation compared to conditioned media from cultures treated with rnTiO2. However, no significant difference was found in the toxicological effects on cell viability of ultra violet irradiated anTiO2 and rnTiO2. In conclusion, our results indicate that anTiO2 is less potent in induction of alveolar macrophage infiltration, 8-OHdG and MIP1??expression in the lung, and growth stimulation of A549 cells in vitro than rnTiO2.
authors.affiliation: Department of Molecular Toxicology, Nagoya City University Graduate School of Medical Sciences and Medical School, Nagoya, Japan E-mail : suzui@med.nagoya-cu.ac.jp.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Numano
authors.forename: Jiegou
authors.initials: J
authors.lastname: Xu
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Futakuchi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fukamachi
authors.forename: David B
authors.initials: DB
authors.lastname: Alexander
authors.forename: Fumio
authors.initials: F
authors.lastname: Furukawa
authors.forename: Jun
authors.initials: J
authors.lastname: Kanno
authors.forename: Akihiko
authors.initials: A
authors.lastname: Hirose
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsuda
authors.forename: Masumi
authors.initials: M
authors.lastname: Suzui
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008168:Lung / Q000166:cytology / Q000187:drug effects*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017319:Photosensitizing Agents / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014025:Titanium / Q000633:toxicity*; D014466:Ultraviolet Rays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C493277:MAPKAP1 protein, human; D017319:Photosensitizing Agents; D012333:RNA, Messenger; C009495:titanium dioxide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D014025:Titanium; D003849:Deoxyguanosine