Islet cell DNA is a target of inflammatory attack by nitric oxide

• Published in: Diabetes (New York, N.Y.) Vol. 42; no. 3; pp. 496 - 500
• Main Authors: Fehsel, K., Jalowy, A., Qi, S., Burkart, V., Hartmann, B., Kolb, H.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01-03-1993
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.42.3.496

Islet cell DNA is a target of inflammatory attack by nitric oxide.
K Fehsel ,
A Jalowy ,
S Qi ,
V Burkart ,
B Hartmann and
H Kolb
Diabetes Research Institute, University of Düsseldorf, Germany.
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.