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Effects of Gadolinium MRI Contrast Agents on DNA Damage and Cell Survival when Used in Combination with Radiation.
Radiation Research ( IF 3.4 ) Pub Date : 2020-08-03 , DOI: 10.1667/rade-20-00008.1
Emily Russell 1, 2 , Stephen J McMahon 1 , Ben Russell 2 , Hibaaq Mohamud 2 , Conor K McGarry 1, 3 , Giuseppe Schettino 2, 4 , Kevin M Prise 1
Affiliation  

Gadolinium is a commonly used contrast agent for magnetic resonance imaging (MRI). The goal of this work was to determine how MRI contrast agents affect radiosensitivity for tumour cells. Using a 225kVp X-ray cabinet source, immunofluorescence and clonogenic assays were performed on six cancer cell lines: lung (H460), pancreas (MiaPaCa2), prostate (DU145), breast (MCF7), brain (U87) and liver (HEPG2). Dotarem® contrast agent, at concentrations of 0.2, 2 and 20 mM, was used to determine its effect on DNA damage and cell survival. Measurements were performed using inductively coupled plasma mass spectrometry (ICP-MS) to determine the amount of gadolinium taken up by each cell line for each concentration. A statistically significant increase in DNA damage was seen for all cell lines at a dose of 1 Gy for concentrations of 2 and 20 mM, at 1 h postirradiation. At 24 h postirradiation, most of the DNA damage had been repaired, with approximately 90% repair for almost all doses of radiation and concentrations of Dotarem. Clonogenic results showed no statistically significant decrease in cell survival for any cell line or concentration. Uptake measurements showed cell line-specific variations in uptake, with MCF7 and HEPG2 cells having a high percentage uptake compared to other cell lines, with 151.4 ± 0.3 × 10–15 g and 194.8 ± 0.4 × 10–15 g per cell, respectively, at 2 mM Dotarem concentration. In this work, a variability in gadolinium uptake was observed between cell lines. A significant increase was seen in initial levels of DNA damage after 1 Gy irradiation for all six cancer cell lines; however, no significant decrease in cell survival was seen with the clonogenic assay. The observation of high levels of repair suggest that while initial levels of DNA damage are increased, this damage is almost entirely repaired within 24 h, and does not affect the ability of cells to survive and produce colonies.



中文翻译:

当与放射线结合使用时,d MRI造影剂对DNA损伤和细胞存活的影响。

d是磁共振成像(MRI)常用的造影剂。这项工作的目的是确定MRI造影剂如何影响肿瘤细胞的放射敏感性。使用225kVp X射线柜源,对六种癌细胞系进行了免疫荧光和克隆形成测定:肺癌(H460),胰腺(MiaPaCa2),前列腺癌(DU145),乳腺(MCF7),脑(U87)和肝癌(HEPG2) 。Dotarem ®造影剂,以0.2,2且20μm浓度中号,用于确定其对DNA损伤和细胞存活的影响。使用电感耦合等离子体质谱法(ICP-MS)进行测量,以确定每种浓度下每个细胞系吸收的g量。在浓度为2和20 m M的1 Gy剂量下,所有细胞系的DNA损伤均具有统计学上的显着增加,照射后1小时。辐照后24小时,大多数DNA损伤已被修复,几乎所有剂量的辐射和Dotarem浓度的修复率约为90%。克隆产生的结果表明,对于任何细胞系或浓度,细胞存活率均无统计学显着下降。摄取测量显示,细胞系特定的摄取变化,与其他细胞系相比,MCF7和HEPG2细胞的摄取率高,每个细胞分别为151.4±0.3×10 –15 g和194.8±0.4×10 –15 g在2 m MDotarem浓度。在这项工作中,在细胞系之间观察到g摄取的变化。在所有6种癌细胞系中,经过1 Gy辐照后,DNA损伤的初始水平均显着增加。然而,克隆形成试验未见细胞存活率显着下降。对高水平修复的观察表明,虽然最初的DNA损伤水平增加了,但这种损伤在24小时内几乎完全被修复,并且不影响细胞存活和产生菌落的能力。

更新日期:2020-09-18
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