School of Physics, University of Sydney, Sydney, NSW 2006, Australia.
Comput Math Methods Med. 2012;2012:147252. doi: 10.1155/2012/147252. Epub 2012 Jun 3.
The long-held view that radiation-induced biological damage must be initiated in the cell nucleus, either on or near DNA itself, is being confronted by mounting evidence to suggest otherwise. While the efficacy of cell death may be determined by radiation damage to nuclear DNA, a plethora of less deterministic biological responses has been observed when DNA is not targeted. These so-called nontargeted responses cannot be understood in the framework of DNA-centric radiobiological models; what is needed are new physically motivated models that address the damage-sensing signalling pathways triggered by the production of reactive free radicals. To this end, we have conducted a series of in silico experiments aimed at elucidating the underlying physical processes responsible for nontargeted biological responses to radiation. Our simulation studies implement new results on very low-energy electromagnetic interactions in liquid water (applicable down to nanoscales) and we also consider a realistic simulation of extranuclear microbeam irradiation of a cell. Our results support the idea that organelles with important functional roles, such as mitochondria and lysosomes, as well as membranes, are viable targets for ionizations and excitations, and their chemical composition and density are critical to determining the free radical yield and ensuing biological responses.
长期以来，人们认为辐射诱导的生物损伤必须在细胞核内启动，要么在 DNA 本身或其附近。但越来越多的证据表明情况并非如此。虽然细胞死亡的效果可能取决于核 DNA 的辐射损伤，但当 DNA 不成为靶标时，已经观察到大量的、非确定性的生物反应。这些所谓的非靶向反应不能用以 DNA 为中心的放射生物学模型来理解；需要的是新的物理驱动模型，以解决由活性自由基产生引发的损伤感应信号通路。为此，我们进行了一系列的计算机模拟实验，旨在阐明导致辐射非靶向生物反应的潜在物理过程。我们的模拟研究实现了关于液体水中极低能电磁相互作用的新结果（适用于纳米尺度以下），并且我们还考虑了对细胞外核微束照射的实际模拟。我们的结果支持这样一种观点，即具有重要功能作用的细胞器，如线粒体和溶酶体以及膜，是离子化和激发的可行靶标，它们的化学组成和密度对于确定自由基产量和随后的生物反应至关重要。
