Environmental noise aggravates oxidative DNA damage, granulocyte oxidative burst and nitrate resistance in Ogg1−/− mice

Abstract

BackgroundLarge epidemiological studies point towards a link between the incidence of arterial hypertension, ischemic heart disease, metabolic disease and exposure to traffic noise, supporting its role as an independent cardiovascular risk factor. We characterized the underlying molecular mechanisms leading to noise‐dependent adverse effects on the vasculature in an animal model of aircraft noise exposure identifying oxidative stress and inflammation as central players in mediating vascular dysfunction. Here, we want to study the impact of noise‐induced oxidative DNA damage on vascular function in DNA‐repair deficient Ogg1−/− (8‐oxoguanine glycosylase knockout) mice.Methods and ResultsOgg1−/− and corresponding wild type mice were exposed to aircraft noise (peak sound levels of 85 dB(A) and mean sound level of 72 dB(A)) for 4 days. We could show that 4 days noise exposure induced significant degree of endothelial dysfunction in wild type and Ogg1−/− mice. In contrast, endothelium‐independent relaxation was only impaired in noise‐exposed Ogg1−/−, indicating the presence of nitrate resistance in noise‐exposed Ogg1−/− mice. The cardioprotective, aldehyde detoxifying enzyme mitochondrial aldehyde dehydrogenase (ALDH‐2), which is necessary for nitroglycerin bioactivation, was upregulated only in the noise‐exposed Ogg1−/− mice, which may indicate the compensatory upregulation of dysfunctional ALDH‐2. Aircraft noise exposure caused oxidative DNA damage (8‐oxo‐deoxyguanosin) and elevated NOX‐2 expression in wild type mice with synergistic increases in Ogg1−/− mice (shown by immunohistochemistry). A similar pattern was found for oxidative burst of blood leukocytes and other markers of oxidative stress (4‐hydroxynonenal, 3‐nitrotyrosine) and inflammation (cyclooxygenase‐2).ConclusionThe finding that chronic noise exposure causes oxidative DNA damage in mice is worrisome since these potential mutagenic lesions could contribute to cancer progression. Human field studies have to demonstrate whether oxidative DNA damage is also found in urban populations with high levels of noise exposure as recently shown for workers with high occupational noise exposure.Support or Funding InformationWe gratefully acknowledge the financial support by the Naturwissenschaftlich‐Medizinisches Forschungszentrum (NMFZ) of the Johannes Gutenberg University Mainz (to B.E. and A.D.), the Boehringer Ingelheim Foundation „Novel and neglected cardiovascular risk factors: molecular mechanisms and therapeutic implications” is gratefully acknowledged (to S.S., T.M. and A.D.) and a postdoctoral research stipend for a scientific stay in Mainz by the Slovak Academy of Science (to M.K.).