gammaH2AX: A potential DNA damage response biomarker for assessing toxicological risk of tobacco products.
gammaH2AX: A potential DNA damage response biomarker for assessing toxicological risk of tobacco products.
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DOI：
10.1016/j.mrgentox.2009.06.009
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发表时间：
2009-08
影响因子：
1.9
通讯作者：
Darzynkiewicz, Zbigniew
中科院分区：
文献类型：
--
作者：
Albino, Anthony P.;Jorgensen, Ellen D.;Rainey, Patrick;Gillman, Gene;Clark, T. Jeffrey;Gietl, Diana;Zhao, Hong;Traganos, Frank;Darzynkiewicz, Zbigniew
美国香烟的区别主要取决于专有烟草混合物、薄荷醇、烟草替代品、纸张孔隙度、纸张添加剂和过滤嘴通风的使用。这些特征实质上改变了政府机构颁布的标准化方案中每支香烟的焦油和尼古丁产量。然而，由于吸烟行为的补偿性改变以维持优选的尼古丁剂量（例如，通过增加抽吸频率、更深地吸入、每天吸更多的香烟或堵塞过滤嘴通风孔），吸烟者实际上吸入相似量的焦油和尼古丁，而不管任何香烟变量，支持流行病学证据，即所有品牌都具有可比的疾病风险。因此，无论香烟结构或吸烟行为的差异如何，开发一种能够真实地比较香烟烟雾（CS）诱导的遗传毒性的检测方法将是有利的。潜在致癌DNA损伤的一个重要指标是双链断裂（DSB），这可以通过测量组蛋白H2 AX上Ser 139磷酸化来监测。以前我们发现暴露的肺细胞中H2 AX（定义为γ H2 AX）的磷酸化与CS剂量成正比。因此，我们建议γ H2 AX可能是一个可行的生物标志物，用于评估与实际尼古丁/焦油输送相关的香烟遗传毒性风险。在这里，我们通过测量暴露于CS的A549人肺细胞中的γ H2 AX水平来验证这一假设，CS来自使用各种吸烟方案的一系列商业香烟。结果表明，γ H2 AX诱导，哺乳动物DNA损伤反应的关键事件，提供了一个评估CS诱导的DNA损伤的吸烟地形或香烟类型无关。我们的结论是，γ H2 AX诱导显示出作为遗传毒性生物测定的前景，提供了特定的优势，比传统的方法，用于评估传统和非传统的烟草产品。
Differentiation among American cigarettes relies primarily on the use of proprietary tobacco blends, menthol, tobacco substitutes, paper porosity, paper additives, and filter ventilation. These characteristics substantially alter per cigarette yields of tar and nicotine in standardized protocols promulgated by government agencies. However, due to compensatory alterations in smoking behavior to sustain a preferred nicotine dose (e.g., by increasing puff frequency, inhaling more deeply, smoking more cigarettes per day, or blocking filter ventilation holes), smokers actually inhale similar amounts of tar and nicotine regardless of any cigarette variable, supporting epidemiological evidence that all brands have comparable disease risk. Consequently, itwould be advantageous to develop assays that realistically compare cigarette smoke (CS)-induced genotoxicity regardless of differences in cigarette construction or smoking behavior. One significant indicator of potentially carcinogenicDNA damage is double strand breaks (DSBs), which can be monitored by measuring Ser 139 phosphorylation on histone H2AX. Previouslywe showed that phosphorylation of H2AX (defined as γH2AX) in exposed lung cells is proportional to CS dose. Thus, we proposed that γH2AX may be a viable biomarker for evaluating genotoxic risk of cigarettes in relation to actual nicotine/tar delivery. Here we tested this hypothesis by measuring γH2AX levels in A549 human lung cells exposed to CS from a range of commercial cigarettes using various smoking regimens. Results show that γH2AX induction, a critical event of the mammalian DNA damage response, provides an assessment of CS-induced DNA damage independent of smoking topography or cigarette type. We conclude that γH2AX induction shows promise as a genotoxic bioassay offering specific advantages over the traditional assays for the evaluation of conventional and nonconventional tobacco products.
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影响因子：
3.8
作者：
Hammond, David;Fong, Geoffrey T.;McNeill, Ann
通讯作者：
McNeill, Ann
影响因子：
4.8
作者：
Furuta, T;Takemura, H;Pommier, Y
通讯作者：
Pommier, Y
影响因子：
64.8
作者：
Bartkova, J;Horejsi, Z;Bartek, J
通讯作者：
Bartek, J
影响因子：
3.4
作者：
Coggins, Christopher R. E.;Gaworski, Charles L.
通讯作者：
Gaworski, Charles L.
影响因子：
6
作者：
Godtfredsen, Nina S.;Prescott, Eva;Osler, Merete
通讯作者：
Osler, Merete