Optical Imaging of PARP1 in Response to Radiation in Oral Squamous Cell Carcinoma.
Optical Imaging of PARP1 in Response to Radiation in Oral Squamous Cell Carcinoma.
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DOI：
10.1371/journal.pone.0147752
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Reiner T
中科院分区：
文献类型：
--
作者：
Kossatz S;Weber WA;Reiner T
靶向和抑制DNA修复途径是控制恶性肿瘤生长的有力策略。一种这样的策略包括抑制PARP 1，PARP 1是细胞内DNA损伤反应中的中心元件。为了确定和可视化PARP 1在体内的表达和细胞间分布，并监测PARP 1靶向治疗剂的药代动力学，开发了荧光小探针。然而，到目前为止，还不清楚这些探针在更现实的临床环境中如何表现，其中DNA损伤已通过一种或多种先前的治疗线诱导。在这里，我们使用这样的成像剂，PARPi-FL，在组织中有和没有先前的DNA损伤，并调查其作为PARP 1成像探针的价值。我们发现PARP 1在口腔癌中的表达是高的，并且PARPi-FL的摄取是选择性的，无论细胞是否暴露于辐射。我们还表明，PARPi-FL摄取增加响应DNA损伤，这种增加反映在更高的酶表达。我们的研究结果提供了一个框架，用于测量细胞暴露于外部束辐射，并可能有助于阐明这种治疗在小鼠癌症模型中的非侵入性效果。
Targeting and inhibiting DNA repair pathways is a powerful strategy of controlling malignant growth. One such strategy includes the inhibition of PARP1, a central element in the intracellular DNA damage response. To determine and visualize the expression and intercellular distribution of PARP1 in vivo, and to monitor the pharmacokinetics of PARP1 targeted therapeutics, fluorescent small probes were developed. To date, however, it is unclear how these probes behave in a more realistic clinical setting, where DNA damage has been induced through one or more prior lines of therapy. Here, we use one such imaging agent, PARPi-FL, in tissues both with and without prior DNA damage, and investigate its value as a probe for PARP1 imaging. We show that PARP1 expression in oral cancer is high, and that the uptake of PARPi-FL is selective, irrespective of whether cells were exposed to irradiation or not. We also show that PARPi-FL uptake increases in response to DNA damage, and that this increase is reflected in higher enzyme expression. Our findings provide a framework for measuring exposure of cells to external beam radiation, and could help to elucidate the effects of such treatments non-invasively in mouse models of cancer.