Hypertensive patients exhibit elevated cancer incidence, especially of cancers of the kidney. Elevated levels of angiotensin II (AngII), 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 AngII is an activator of NAD(P)H oxidase, leading to the formation of free radical, which is known to participate in the induction of DNA damage. This study was undertaken to characterise AngII-induced DNA damage. DNA damage was measured by comet assay and micronucleus frequency test. Incubation of pig kidney cells (LLC-PK1) in vitro with AngII concentrations between 85 and 340 nM led to a 6- to 15-fold increase of DNA damage compared to the control as revealed by comet assay analysis. Micronuclei were induced approximately 4-fold compared to the control in pig and rat kidney cells (LLC-PK1, NRK) and in human promyelocytic cells (HL-60). AngII-induced DNA damage could be prevented by co-incubation with the AngII type 1 receptor blocker candesartan and the antioxidants N-acetylcysteine and -tocopherol. The AngII type 2 receptor antagonist PD123319 could not reduce AngII-induced DNA damage. Measurement of reactive oxygen species (ROS) by flow cytometry showed an enhanced formation after exposure to AngII and a reduction of ROS after candesartan, N-acetylcysteine and -tocopherol. The present findings support our hypothesis that AngII causes DNA damage via AngII type 1 receptor binding and subsequent formation of oxidative stress.