Table 2.
Tumour microenvironment inflammatory mediators modulated by IR
| Mediators | Source | Dose/fraction | Tissue niche | References |
|---|---|---|---|---|
| Transcription factors | ||||
| NF-κB | α-particle (241Am) | 1 Gy/1fx | Human bronchial epithelial cells (Beas-2B) conditioned media on macrophage cells (U937) | Fu et al. (2016) |
| NF-κB, AP-1, Sp-1, p53 | γ-ray (137Cs) | 5–30 Gy/1fx | Rat cerebral cortex | Raju et al. (2000) |
| NF-κB, AP-1, CREB | γ-ray (137Cs) | 10 Gy/1fx | Rat brain | Lee et al. (2010) |
| STAT-3 | γ-ray (60Co) | 2–10 Gy/1fx | Human alveolar carcinoma cells (A549) | Gao et al. (2014) |
| NF-κB | α-particle (3He) microbeam | 0.5 Gy/1fx | Human skin and lung fibroblasts | Zhou et al. (2008) |
| NF-κB | X-ray | 2–8 Gy/1fx | Murine microglia cells (BV-2) | Hwang et al. (2006) |
| Tyrosine/protein kinases | ||||
| PKCβII | γ-ray (137Cs) | 1 Gy/1fx or 10 Gy/1fx | Human lung fibroblast (MRC-5) | Baskar et al. (2008) |
| Raf-1, MAPK, PKCγ, PLC, IP3 | γ-ray (60Co) | 2 Gy/1fx | Human squamous carcinoma cells (A431) | Dent et al. (2003) |
| MAPK, JNK, ERK, p38 | α-particle (241Am) | 1 Gy/1fx | Human bronchial epithelial cells (Beas-2B) conditioned media on macrophage cells (U937) | Fu et al. (2016) |
| Tumour suppressor | ||||
| p53 | γ-ray (137Cs) | 5–30 Gy/1fx | Rat cerebral cortex | Raju et al. (2000) |
| Pro-inflammatory cytokines | ||||
| IL-1β, TNF-α, IL-16 | ? | ? hypo versus hyper fx | Mouse colon | Barlow et al. (2016) |
| IL-1α, IL-1β, TNF-α | X-ray versus γ-ray (137Cs) | 7–25 Gy/1fx | Mouse brain | Hong et al. (1995) |
| IL-β, TNF-α | γ-ray (137Cs) | 10 Gy/1fx | Rat brain | Lee et al. (2010) |
| IL-6 | γ-ray (60Co) | 10 Gy/1fx | Human alveolar carcinoma cells (A549) | Gao et al. (2014) |
| IL-1β, TNF-α | α-particle (3He) microbeam | 0.5 Gy/1fx | Human lung fibroblasts | Zhou et al. (2008) |
| IL-6 | γ-ray (60Co or 137Cs) | 9–10 Gy/1fx | Mouse plasma and lung | Van der Meeren et al. (2003) |
| TNF-α | γ-ray (192Ir) | 10 Gy/1fx | Rat brain | (Kim et al. 2002) |
| IL-1α, TNF-α | γ-ray (137Cs) | 0–35 Gy/1fx | Mouse brain | Moravan et al. (2011) |
| TNF-α | X-ray | 2–20 Gy/1fx versus 10–40 Gy/5–20fx | Mouse brain | Gaber et al.(2003) |
| IL-1α, IL-6 | X-ray | 12 Gy/1fx | Mouse lung, bronchial lavage fluid, serum | Ao et al. (2009) |
| IL-8 | α-particle (238Pu) | 0.036–0.19 Gy/1fx | Human lung fibroblasts | Narayanan et al. (1999) |
| IL-1α, IL-1β, IL12p40, IL-18, TNF-α, IFN-γ | γ-ray (60Co) | 5–20 Gy/1fx | Murine bone marrow-derived macrophages | Liu et al. (2017) |
| Anti-inflammatory cytokines | ||||
| TGF-β1 | γ-ray (192Ir) | 10 Gy/1fx | Rat brain | Kim et al. (2002) |
| IL-4, IL-5, IL-10 | γ-ray (60Co) | 5 Gy/1fx | Murine splenocytes | Han et al. (2006) |
| Haematopoietic | ||||
| EPO, TPO | γ-ray (60Co) | 7.5 Gy/1fx | Mouse plasma and kidney | Barshishat-Kupper et al. (2011) |
| G-CSF | X-ray | 12 Gy/1fx | Mouse lung, bronchial lavage fluid, serum | Ao et al. (2009) |
| EPO | γ-ray (137Cs) | 4 Gy/1fx | Mouse plasma | Peslak et al. (2012) |
| CSF1, IL-34 | X-ray | 12 Gy/1fx | Patient-derived xenografts (U251, GBM12) | Stafford et al. (2016) |
| Prostanoids | ||||
| PGE2 and TXA2 | γ-ray (137Cs) | 35 Gy/1fx | Mouse brain | Moore et al. (2004) |
| PTGES | γ-ray (137Cs) | 0–35 Gy/1fx | Mouse brain | Moravan et al. (2011) |
| Growth factors | ||||
| EGFR | γ-ray (137Cs) | 2 Gy/1fx | Human breast (MDA-MB-231) and squamous carcinoma cells (A431) | Dent et al. (2003) |
| EGFR | γ-ray (60Co) | 10 Gy/1fx | Human alveolar carcinoma cells (A549) | Gao et al. (2014) |
| Basic FGF | γ-ray (137Cs) | 10 Gy/1fx | Rat cerebral cortex | Raju et al. (2000) |
| VEGF | X-ray | 6 Gy/3fx | Rat cerebral cortex | Jin et al. (2014) |
| G-CSF | X-ray | 12 Gy/1fx | Mouse lung, bronchial lavage fluid, serum | Ao et al. (2009) |
| Chemokines | ||||
| CXCL10 | ? | ? hypo versus hyper fx | Mouse colon cancer cells (Colon 38) | Barlow et al. (2016) |
| CCL2 | γ-ray (137Cs) | 10 Gy/1fx | Rat brain | Lee et al. (2010) |
| CXCL1 | γ-ray (60Co or 137Cs) | 9–10 Gy/1fx | Mouse plasma and lung | Van der Meeren et al. (2003) |
| CCL2 | γ-ray (137Cs) | 0–35 Gy/1fx | Mouse brain | Moravan et al. (2011) |
| CXCL1, CCL2, CXCL10 | X-ray | 12 Gy/1fx | Mouse lung, bronchial lavage fluid, serum | Ao et al. (2009) |
| CCL2 | γ-ray (60Co) | 5–20 Gy/1fx | Murine bone marrow-derived macrophages | Liu et al. (2017) |
| Adhesion molecules | ||||
| ICAM-1 | X-ray versus γ-ray (137Cs) | 2–25 Gy/1fx | Mouse brain | Hong et al. (1995) |
| P-selectin, PECAM-1 | γ-ray (60Co or 137Cs) | 9–10 Gy/1fx | Mouse lung endothelial cells | Van der Meeren et al. (2003) |
| ICAM-1 | γ-ray (137Cs) | 0–35 Gy/1fx | Mouse brain | Moravan et al. (2011) |
| ICAM-1 | X-ray | 2–20 Gy/1fx versus 10–40 Gy/5–20fx | Mouse brain | Gaber et al. (2003) |
| P-selectin, VCAM-1 | γ-ray (137Cs) | 9 Gy/1fx | Mouse bone marrow | Mazo et al. (2002) |
| Enzymes | ||||
| COX-2, iNOS | α-particle (3He) microbeam | 0.5 Gy/1fx | Human skin and lung fibroblasts | Zhou et al. (2008) |
| COX-2 | X-ray | 15 Gy/1fx | Murine microglial cells (BV-2) | Hwang et al. (2006) |
| COX-2 | γ-ray (137Cs) | 35 Gy/1fx | Mouse brain | Moore et al. (2004) |
| COX-1, COX-2, HO-1, caspase-1, GSTP-1, SOD2 | γ-ray (137Cs) | 0–35 Gy/1fx | Mouse Brain | Moravan et al. (2011) |
| SOD2, GST, GPX and catalase | γ-ray (137Cs) | 0.02 Gy/fx | Human lymphoblastoid cells (AHH-1) | Bravard et al. (1999) |
| HO-1,GSTA-2 | γ-ray (137Cs) | 2.5–20 Gy/5fx | Murine embryo fibroblasts, fibroblast cells (NIH-3T3) and dendritic cells (DC2.4) | McDonald et al. (2010) |
| HO-1 | γ-ray (137Cs) | 0.1–2.5 Gy/1fx | Mouse macrophages cells (RAW264.7) | Tsukimoto et al. (2010) |
| Angiogenic/vascular | ||||
| VEGF | X-ray | 6 Gy/3fx | Mouse brain | Jin et al. (2014) |
| HIF-1α and HIF-2α | γ-ray (60Co) | 7.5 Gy/1fx | Mouse plasma and kidney | Barshishat-Kupper et al. (2011) |
| Basic FGF | γ-ray (137Cs) | 10 Gy/1fx | Rat cerebral cortex | Raju et al. (2000) |
| Pro-fibrotic | ||||
| TGF-β1 | γ-ray (192Ir) | 10 Gy/1fx | Rat brain | Kim et al. (2002) |
| TGF-β1 | Proton (3He) microbeam | 0.016–0.16 Gy/1fx | Human glioblastoma cells (T98G) | Shao et al. (2008) |
| Acute phase proteins | ||||
| Alpha 1-antichymotrypsin | X-ray versus γ-ray (137Cs) | 25 Gy/1fx | Mouse brain | Hong et al. (1995) |
| Hypoxia-sensing proteins | ||||
| HIF-1α and HIF-2α | γ-ray (60Co) | 7.5 Gy/1fx | Mouse plasma and kidney | Barshishat-Kupper et al. (2011) |
| Coagulation | ||||
| Factors II, V, VII, VIII, IX, X, XI, XII | Proton | 0–2 Gy/1fx high- versus low-dose rate | Ferret plasma | Krigsfeld et al. (2012) |
| TF, endothelial microparticles | X-ray | 20 Gy/1fx | Human PBMC | Goldin-Lang et al. (2007) |
| TF, TM | γ-ray (60Co or 137Cs) | 9–10 Gy/1fx | Mouse plasma and lung endothelial cells | Van der Meeren et al. (2003) |
| TM, PAR-1 | X-ray | 33.6 Gy/8fx or 67.2/16fx | Rat intestinal vascular and smooth muscle cells | Wang et al. (2002) |
AP activator protein, COX cyclo-oxygenase, CREB cyclic adenosine monophosphate responsive element binding protein, CSF colony stimulating factor, EGF epidermal growth factor, EGR early growth response protein, EPO erythropoietin, FGF fibroblast growth factor, G-CSF granulocyte colony stimulating factor, GM-CSF granulocyte/macrophage colony stimulating factor, GPX glutathione peroxidase, GST glutathione S-transferase, HIF hypoxia-inducible factor, HO heme oxygenase, ICAM intercellular cell adhesion molecule, NF-κB nuclear factor-κB, PECAM platelet endothelial cell adhesion molecule, PG prostaglandin, PI3K phosphoinositide 3-kinase, SOD superoxide dismutase, SP specificity protein, STAT signal transducer and activator of transcription, TPO thyroid peroxidase, TX thromboxane, VCAM vascular cell adhesion molecule, VEGF vascular endothelial growth factor