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Angiotensin II Induces DNA Damage in the Kidney
- Source :
- Cancer Research. 68:9239-9246
- Publication Year :
- 2008
- Publisher :
- American Association for Cancer Research (AACR), 2008.
-
Abstract
- Increased activity of the renin angiotensin system with enhanced levels of angiotensin II leads to oxidative stress with endothelial dysfunction, hypertension, and atherosclerosis. Epidemiologic studies revealed a higher cancer mortality and an increased kidney cancer incidence in hypertensive patients. Because elevated angiotensin II levels might contribute to carcinogenesis, we tested whether angiotensin II induces DNA damage in the kidney. In isolated perfused mouse kidneys, as little as 1 nmol/L angiotensin II caused a significant increase in DNA strand breaks, measured with the comet assay. This damage was independent of the hemodynamic effect of angiotensin II and mediated by the angiotensin II type 1 receptor. Angiotensin II also caused double-strand breaks in the cells of the isolated perfused kidney, detected with an antibody against the double-strand break marker γ-H2AX. Studies in cell culture allowed further characterization of the DNA damage induced by angiotensin II. Single- and double-strand breaks, abasic sites, and 7,8-dihydro-8-oxo-guanine, all types of oxidative DNA lesions, were detected in angiotensin II–treated renal cells. The majority of detected strand breaks was repaired within 1 hour, but double-strand breaks increased and persisted for at least 24 hours. [Cancer Res 2008;68(22):9239–46]
- Subjects :
- Male
Cancer Research
medicine.medical_specialty
Swine
DNA damage
Apoptosis
Kidney
medicine.disease_cause
Histones
Mice
Internal medicine
Renin–angiotensin system
medicine
Animals
DNA Breaks, Double-Stranded
Angiotensin II receptor type 1
Dose-Response Relationship, Drug
biology
Angiotensin II
Angiotensin-converting enzyme
Flow Cytometry
Mice, Inbred C57BL
Comet assay
Endocrinology
medicine.anatomical_structure
Oncology
biology.protein
LLC-PK1 Cells
Oxidative stress
DNA Damage
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 68
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....237049ad2671529be524b6ecb8f75022