title: Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats.
abstract: Chrysotile (CH) is a pathogenic waste building material that can potentially be rendered innocuous via conversion to forsterite (FO) by heating at high temperatures. We compared the ability of FO and CH to cause oxidative DNA damage and lung injury. A single 1-mg intratracheal dose of CH or FO was administered to rats. Significant changes were observed 3 to 7 days after CH injection in alveolar macrophages, neutrophils, eosinophils, lymphocytes, total protein, and lactate dehydrogenase. High concentrations of 8-hydroxy-29-deoxyguanosine (8-OHdG) were also observed in the macrophages, other infiltrating inflammatory cells, granulomas, and in bronchiolar and alveolar epithelial cells. The overexpression of 8-OHdG was limited to airway epithelial and inflammatory cells surrounding the fibrotic foci 540 days after injection, indicating that the inflammatory effects of CH were persistent yet decreased with time. Compared to the CH group, acute lung inflammation observed in the FO group was less apparent and exhibited no progressive fibrosing lesions. The expression of 8-OHdG was transient and weak in the bronchiolar epithelial cells as well as in the inflammatory cells, consistent with low concentrations of 8-OHdG observed in the lungs. These findings confirm that FO causes significantly less inflammation and oxidative DNA damage in the lungs than CH.
authors: Department of Preventive Medicine, St. Marianna University School of Medicine, Kawasaki, Japan. ayakot@marianna-u.ac.jp
authors: Ayako
authors: A
authors: Takata
authors: Hiroshi
authors: H
authors: Yamauchi
authors: Tadao
authors: T
authors: Toya
authors: Masahito
authors: M
authors: Aminaka
authors: Yasushi
authors: Y
authors: Shinohara
authors: Norihiko
authors: N
authors: Kohyama
authors: Katsumi
authors: K
authors: Yoshida
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D017632:Asbestos, Serpentine / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D007442:Intubation, Intratracheal; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008274:Magnesium; D008297:Male; D010084:Oxidation-Reduction; D011506:Proteins / Q000032:analysis; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017655:Silicon Compounds / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D017632:Asbestos, Serpentine; D011506:Proteins; D017655:Silicon Compounds; C503823:forsterite; D000080242:8-Hydroxy-2'-Deoxyguanosine; D007770:L-Lactate Dehydrogenase; D003849:Deoxyguanosine; D008274:Magnesium