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This Article Full Text Full Text (PDF) All Versions of this Article: 292/5/F1427    most recent 00458.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Schupp, N. Articles by Stopper, H. Search for Related Content PubMed PubMed Citation Articles by Schupp, N. Articles by Stopper, H.

Angiotensin II-induced genomic damage in renal cells can be prevented by angiotensin II type 1 receptor blockage or radical scavenging

¹Institute of Pharmacology and Toxicology, and ³Department of Internal Medicine, University of Würzburg, Würzburg, Germany; and ²Department of Nephrology Transplantology and Internal Diseases, Medical University, Gdansk, Poland

Submitted 16 November 2006 ; accepted in final form 9 January 2007

Hypertensive patients exhibit elevated cancer incidence, especially of cancers of the kidney. Elevated levels of ANG II, the active peptide of the renin-angiotensin system, regulating blood pressure and cardiovascular homeostasis, are known to cause hypertension and kidney diseases. There is evidence that ANG II is an activator of NAD(P)H oxidase, leading to the formation of free radicals, which are known to participate in the induction of DNA damage. This study was undertaken to characterize ANG II-induced DNA damage. DNA damage was measured by comet assay and micronucleus frequency test. Incubation of pig kidney cells (LLC-PK₁) in vitro with ANG II concentrations between 85 and 340 nM led to a 6- to 15-fold increase of DNA damage compared with the control as revealed by comet assay analysis. Micronuclei were induced about fourfold compared with the control in pig and rat kidney cells (LLC-PK₁, NRK) and in human promyelocytic cells (HL-60). ANG II-induced DNA damage could be prevented by coincubation with the ANG II type 1 receptor blocker candesartan and the antioxidants N-acetylcysteine and -tocopherol. The ANG II type 2 receptor antagonist PD123319 could not reduce ANG II-induced DNA damage. Measurement of reactive oxygen species (ROS) by flow cytometry showed an enhanced formation after exposure to ANG II and a reduction of ROS after candesartan, N-acetylcysteine, and -tocopherol. The present findings support our hypothesis that ANG II causes DNA damage via ANG II type 1 receptor binding and subsequent formation of oxidative stress.

kidney cells; deoxyribonucleic acid damage; oxidative stress; candesartan; N-acetylcysteine

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