Production of early and late nuclear DNA damage and extracellular 8-oxodG in normal human skin fibroblasts after carbon ion irradiation compared to X-rays. (October 2018)

• Record Type: Journal Article
• Authors: Prevost, Virginie; Sichel, François; Pottier, Ivannah; Leduc, Alexandre; Lagadu, Stéphanie; Laurent, Carine
• Is Part Of: Toxicology in vitro. Volume 52(2018)
• Page Start: 116
• Page End: 121
• Publication Date: 2018-10
• Subjects: 8-oxodG 8-oxo-7, 8-dihydro-2′-deoxyguanosine -- C-ions carbon ions -- HPLC-ECD High-performance liquid chromatography coupled with electrochemical detection -- LET Linear Energy Transfer -- OTM Olive Tail Moment -- RBE Relative Biologial Efficiency -- ROS Reactive Oxygen Species -- SOBP Spread-Out Bragg Peak -- SPE Solid-Phase Extraction; DNA damage -- Oxidative stress -- Carbon ions -- Skin -- 8-oxodG; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2018.06.004
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: This work aims to evaluate genotoxicity of C-ion vs. X-ray irradiation in normal human skin fibroblasts. Clonogenic cell survival was first evaluated using a linear-quadratic model. Then, early and late genotoxicity was quantified by alkaline comet assay, micronucleus test and 8-oxodG extracellular measurement. Survival strongly decreased after C-ions compared to X-rays with a 4.8-fold decrease at D0 – irradiation dose corresponding to 37% of survival. The level of immediate DNA damage was approximately the same after C-ions or X-rays. However, half-time of DNA repair was 1.3-fold decreased after C-ions compared to X-rays leading to a 2.2-fold increase in remaining damage. In the same way, micronucleus formation was 1.7-fold increased 24 h after irradiation and remained 1.8-fold increased 2 weeks after C-ions vs. X-rays when secondary oxidative stress wave occurred. This was related to a 2.6-fold increase in binucleated cells percentage in carbon- vs. X-ray-irradiated fibroblasts. Excretion of 8-oxodG was also 1.5–fold increased after C-ions vs. X-rays. 8-oxodG excretion could therefore participate to the appearance of late waves of oxidative stress. These results showed a stronger genotoxicity of C-ions in skin fibroblasts. More investigations are needed to clarify the discrepancy between the two types of radiations. Highlights: More remaining skin DNA damage after carbon ion vs. X-ray irradiation were observed. Excretion of 8-oxodG in supernatant was increased after carbon ions vs. X-rays. Genotoxicity was stronger in skin fibroblasts exposed to carbon ions vs. X-rays.