Background: Large epidemiological studies point towards a link between the incidence of arterial hypertension, ischaemic heart disease, metabolic disease and exposure to traffic noise, supporting the role of noise exposure as an independent cardiovascular risk factor. We characterised the underlying molecular mechanisms leading to noise-dependent adverse effects on the vasculature and myocardium in an animal model of aircraft noise exposure and identified oxidative stress and inflammation as central players in mediating vascular and cardiac dysfunction. Here, we studied the impact of noise-induced oxidative DNA damage on vascular function in DNA-repair deficient 8-oxoguanine glycosylase knockout (Ogg1^–/–) mice.

Methods and results: Noise exposure (peak sound levels of 85 and mean sound level of 72 dB(A) applied for 4d) caused oxidative DNA damage (8-oxoguanine) and enhanced NOX-2 expression in C57BL/6 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). We observed additive impairment of noise exposure and genetic Ogg1 deficiency on endothelium-independent relaxation (nitroglycerine), which may be due to exacerbated oxidative DNA damage leading to leukocyte activation and oxidative aldehyde dehydrogenase inhibition.

Conclusions: The 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.

背景：大量的流行病学研究表明，动脉高血压，局部缺血性心脏病，代谢性疾病和交通噪声暴露之间存在联系，从而支持了噪声暴露作为独立的心血管危险因素的作用。我们表征了潜在的分子机制，导致飞机噪声暴露的动物模型中对血管和心肌的噪声依赖性不利影响，并确定了氧化应激和炎症是介导血管和心脏功能障碍的主要因素。在这里，我们研究了噪声引起的氧化DNA损伤对DNA修复缺陷型8-氧鸟嘌呤糖基化酶敲除（Ogg1 ^{– / –}）小鼠血管功能的影响。

方法和结果：噪声暴露（峰值声级为85，平均声级为72 dB（A）施加4d）导致C57BL / 6小鼠氧化DNA损伤（8-氧代鸟嘌呤）并增强NOX-2表达，并协同增加。Ogg1 ^{– / –}小鼠（通过免疫组织化学显示）。发现血液白细胞的氧化爆发和氧化应激的其他标志物（4-羟基壬烯醛，3-硝基酪氨酸）和炎症（环氧合酶-2）的模式相似。我们观察到噪声依赖性和内皮非依赖性松弛（硝酸甘油）的遗传Ogg1缺乏的累加性损害，这可能是由于加剧的氧化DNA损伤导致白细胞活化和氧化醛脱氢酶抑制所致。

结论：慢性噪声暴露会导致小鼠氧化性DNA损伤，这一发现令人担忧，因为这些潜在的诱变性损伤可能会导致癌症进展。人体研究必须证明，在高噪声暴露水平的城市人口中是否也发现了氧化DNA损伤，正如最近对高职业噪声暴露的工人所显示的那样。