Abstract
Breast cancer remains a major concern and its physiopathology is influenced by iodine deficiency (ID) and radiation exposure. Since radiation and ID can separately induce oxidative stress (OS) and microvascular responses in breast, their combination could additively increase these responses. Therefore, ID was induced in MCF7 and MCF12A breast cell lines by medium change. Cells were then X-irradiated with doses of 0.05, 0.1, or 3 Gy. In MCF12A cells, both ID and radiation (0.1 and 3 Gy) increased OS and vascular endothelial growth factor (VEGF) expression, with an additive effect when the highest dose was combined with ID. However, in MCF7 cells no additive effect was observed. VEGF mRNA up-regulation was reactive oxygen species (ROS)-dependent, involving radiation-induced mitochondrial ROS. Results on total VEGF mRNA hold true for the pro-angiogenic isoform VEGF165 mRNA, but the treatments did not modulate the anti-angiogenic isoform VEGF165b. Radiation-induced antioxidant response was differentially regulated upon ID in both cell lines. Thus, radiation response is modulated according to iodine status and cell type and can lead to additive effects on ROS and VEGF. As these are often involved in cancer initiation and progression, we believe that iodine status should be taken into account in radiation prevention policies.
Highlights
The human population is constantly exposed to diverse types of radiation through natural sources such as UV, radioactive materials from earth or cosmic rays; or through man-made sources mainly from medical exposure [1,2]
Short experimental durations were used because iodine deficiency (ID) was previously shown to increase vascular endothelial growth factor (VEGF) from 3 to 6 h after medium change in these cell lines [33]
In iodine-sufficient conditions, the two highest radiation doses (0.1 and 3 Gy) induced a similar increase in VEGF mRNA expression in MCF12A cells at 4 h (Figure 1), but not in MCF7 cells, while the 0.05 Gy dose had no effect in both cell lines
Summary
The human population is constantly exposed to diverse types of radiation through natural sources such as UV, radioactive materials from earth or cosmic rays; or through man-made sources mainly from medical exposure [1,2]. Several studies demonstrated radiation-induced increases in VEGF expression in vivo and in vitro in diverse organs and cell lines, among which were breast cell lines [6,7,8]. Ionizing radiation is known to increase ROS production through different mechanisms, such as radiolysis of water, mitochondrial disruption or the activation of ROS-producing enzymes [2,12,13,14], and VEGF expression is known to be regulated by ROS content and oxidative stress (OS) via, for instance, ROSand oxidative stress (OS)-sensitive transcription factors [15,16]. By increasing either the activity or the expression of antioxidant enzymes, cells try to regulate the sudden burst in cellular ROS and their consequences, thereby potentially leading to radiation resistance [17,18,19]. Increasing results tend to disagree with this model, and fundamental research is needed to assess low dose radiation effects [20,22,23,24]
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