title: In vivo genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure.
abstract: Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells in vivo, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m(3)), low (0.17 mg/m(3)), middle (0.49 mg/m(3)), and high (0.96 mg/m(3)) dose group, and exposed to MWCNTs via nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (p < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (p < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H2O2 levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (p < 0.05). Conversely, the female rats showed no changes in the H2O2 levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.
authors.affiliation: Bioconvergence Department, Korea Conformity Laboratories , Incheon , Korea .
authors.forename: Jin Sik
authors.initials: JS
authors.lastname: Kim
authors.forename: Jae Hyuck
authors.initials: JH
authors.lastname: Sung
authors.forename: Byung Gil
authors.initials: BG
authors.lastname: Choi
authors.forename: Hyeon Yeol
authors.initials: HY
authors.lastname: Ryu
authors.forename: Kyung Seuk
authors.initials: KS
authors.lastname: Song
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Shin
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Lee
authors.forename: Joo Hwan
authors.initials: JH
authors.lastname: Hwang
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.forename: Gun Ho
authors.initials: GH
authors.lastname: Lee
authors.forename: Kisoo
authors.initials: K
authors.lastname: Jeon
authors.forename: Kang Ho
authors.initials: KH
authors.lastname: Ahn
authors.forename: Il Je
authors.initials: IJ
authors.lastname: Yu
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D020552:Comet Assay; D016207:Cytokines / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D037742:Nanotubes, Carbon / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000378:metabolism; D059551:Toxicity Tests, Subacute
chemical_list: D016207:Cytokines; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species