title: Effects of exposure to nanoparticle-rich diesel exhaust on 8-OHdG synthesis in the mouse asthmatic lung.
abstract: It has been demonstrated that exposure to diesel exhaust (DE) is associated with the induction and exacerbation of respiratory disorders; however, the impacts of DE containing mainly nanoparticles have been less studied. We have previously demonstrated that inhalation exposure to nanoparticle-rich DE (NR-DE) exacerbated allergic pulmonary inflammation, in the context of enhanced local expression of proinflammatory molecules. However, the underlying mechanisms have not been fully elucidated. 8-Hydroxydeoxyguanosine (8-OHdG) is a marker of oxidative damage, particularly in DNA. This study examined the effects of NR-DE on 8-OHdG synthesis in the lung in the presence or absence of an allergen. Institute for Cancer Research (ICR) mice were exposed by inhalation to four different gas compositions (control air, low-concentration DE, high-concentration DE and high-concentration DE without particulate matter) for 8 weeks, in the presence or absence of repetitive intratracheal administration of ovalbumin (OVA). Thereafter, we assessed the levels of 8-OHdG synthesis and expression in the lungs by means of enzyme immunoassay (EIA) and immunohistochemistry. The EIA revealed that the level of 8-OHdG was significantly higher in the high-concentration NR-DE-exposed and allergen-sensitized/stimulated group compared with that in the control air-exposed and allergen-treated group. The immunohistochemistry results demonstrated that the level of immunoreactive 8-OHdG was higher in the NR-DE-exposed and allergen-treated lungs compared with that in the corresponding control air-exposed lungs. The results suggested that NR-DE exposure enhanced 8-OHdG formation in asthmatic lungs. This, at least in part, is involved in the NR-DE-mediated exacerbation of the allergic pathophysiology that was identified in our previous study.
authors.affiliation: Center for Medical Science, International University of Health and Welfare, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Tanaka
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Seishiro
authors.initials: S
authors.lastname: Hirano
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.forename: Akinori
authors.initials: A
authors.lastname: Shimada
authors.forename: Ken-Ichiro
authors.initials: KI
authors.lastname: Inoue
keywords: 8-OHdG; allergic pulmonary inflammation; nanoparticle-rich diesel exhaust; oxidative stress