title: Gene expression profiles in rat lung after inhalation exposure to C60 fullerene particles.
abstract: Concern over the influence of nanoparticles on human health has risen due to advances in the development of nanotechnology. We are interested in the influence of nanoparticles on the pulmonary system at a molecular level. In this study, gene expression profiling of the rat lung after whole-body inhalation exposure to C(60) fullerene (0.12mg/m(3); 4.1x10(4) particles/cm(3), 96nm diameter) and ultrafine nickel oxide (Uf-NiO) particles (0.2mg/m(3); 9.2x10(4) particles/cm(3), 59nm diameter) as a positive control were employed to gain insights into these molecular events. In response to C(60) fullerene exposure for 6h a day, for 4 weeks (5 days a week), C(60) fullerene particles were located in alveolar epithelial cells at 3 days post-exposure and engulfed by macrophages at both 3 days and 1 month post-exposures. Gene expression profiles revealed that few genes involved in the inflammatory response, oxidative stress, apoptosis, and metalloendopeptidase activity were up-regulated at both 3 days and 1 month post-exposure. Only some genes associated with the immune system process, including major histocompatibility complex (MHC)-mediated immunity were up-regulated. These results were significantly different from those of Uf-NiO particles which induced high expression of genes associated with chemokines, oxidative stress, and matrix metalloproteinase 12 (Mmp12), suggesting that Uf-NiO particles lead to acute inflammation for the inhalation exposure period, and the damaged tissues were repaired in the post-exposure period. We suggest that C(60) fullerene might not have a severe pulmonary toxicity under the inhalation exposure condition.
authors.affiliation: Health Technology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Onogawa 16-1, Tsukuba, Ibaraki 305-8569, Japan. ka-fujita@aist.go.jp
authors.forename: Katsuhide
authors.initials: K
authors.lastname: Fujita
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Ogami
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Myojyo
authors.forename: Isamu
authors.initials: I
authors.lastname: Tanaka
authors.forename: Manabu
authors.initials: M
authors.lastname: Shimada
authors.forename: Wei-Ning
authors.initials: WN
authors.lastname: Wang
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Endoh
authors.forename: Kunio
authors.initials: K
authors.lastname: Uchida
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakazato
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fukui
authors.forename: Masanori
authors.initials: M
authors.lastname: Horie
authors.forename: Yasukazu
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Junko
authors.initials: J
authors.lastname: Nakanishi
mesh_terms: D000818:Animals; D001822:Body Burden; D037741:Fullerenes / Q000493:pharmacokinetics / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053758:Nanoparticles; D009532:Nickel / Q000493:pharmacokinetics / Q000633:toxicity; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D037741:Fullerenes; D009532:Nickel; C028007:nickel monoxide; C069837:fullerene C60