title: Islet cell DNA is a target of inflammatory attack by nitric oxide.
abstract: NO has been identified recently as the prime islet-toxic product of inflammatory macrophages. The adverse effects of IL-1 on isolated islets also have been reported to involve NO. We now show that exposure of an islet cell suspension to the NO donor nitroprusside or to activated macrophages leads to DNA strand breaks. Macrophages did not induce DNA damage in the presence of the NO synthase inhibitor NG-methyl-L-arginine. DNA strand breaks were demonstrated at the level of single cells by a modified nick-translation procedure and confirmed by analysis of DNA fragmentation by gel electrophoresis. DNA strand breaks occurred within 1 h and preceded islet cell lysis. DNA damage could not be prevented by inhibitors of endogenous endonucleases. We conclude that islet cell DNA is an early target of NO action.
authors.affiliation: Diabetes Research Institute, University of Düsseldorf, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Fehsel
authors.forename: A
authors.initials: A
authors.lastname: Jalowy
authors.forename: S
authors.initials: S
authors.lastname: Qi
authors.forename: V
authors.initials: V
authors.lastname: Burkart
authors.forename: B
authors.initials: B
authors.lastname: Hartmann
authors.forename: H
authors.initials: H
authors.lastname: Kolb
mesh_terms: D000818:Animals; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004587:Electrophoresis, Agar Gel; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D009569:Nitric Oxide / Q000633:toxicity*; D009599:Nitroprusside / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009599:Nitroprusside; D009569:Nitric Oxide; D004247:DNA