Table 1. Candidate genes involved in the pathogenesis of radiation toxicity.
| Mechanism | examples of genes involved | Refs |
|---|---|---|
| DNA damage repair | ||
| Damage sensing | MRE11A, RAD50, NBN, H2AFX, TP53BP1, BRCA1, MDC1 | 16,17 |
| Mediator proteins | RB1, cyclins (e.g. CCNE1, CCND1, CCNB1), CDKs (e.g. CDK7, CDK10) | 16,17 |
| Cell cycle checkpoint control | CDK inhibitors (e.g. CDKN2C, CCKND2), ATM, ATR, TP53, CHEK2 | 16,17 |
| NHEJ | XRCC6, XRCC5, PRKDC, XRCC4, LIG4 | 16,17 |
| HR | RAD51, BRCA1, BRCA2, XRCC3 | 16,17 |
| Base excision repair | XRCC1, APEX, OGG1 | 16,17 |
| Radiation fibrogenesis | ||
| Apoptosis | TP53, BCL2, caspases (e.g. CASP3), BIRC5, RHOB, TP53INP1 | 18,19 |
| Pro-inflammatory cytokines | TNF, IL1A, IL6 | 18,19 |
| Pro-fibrotic proteins | TGFB1, TGFB2, TGFB3, CTGF | 5 |
| Smad signalling pathway | Receptor-regulated SMADs (SMAD1, SMAD2, SMAD3, SMAD5, SMAD8) | 5 |
| DNA-binding TFs, co-regulators and co-receptors | Type I receptor (SMAD4), inhibitory sMADs (SMAD6,SMAD7), NFKB1 | 5 |
| Increased ECM and collagen deposition | TGF transmembrane receptors TGFBR1 and TGFBR2 | 5 |
| Oxidative stress | ||
| Antioxidant enzymes | Superoxide dismutases (e.g. SOD1) | 20 |
| Renin-angiotensin system | AGT | 21 |
| Endothelial cell damage | ||
| Chemokines recruiting monocytes | Rho proteins, Rho kinases, CTGF, HSP27, ZYX | 22,23 |
| Cytokines | FGF2 | 22,23 |
| Growth factors | VEGF | 22,23 |
AGT, angiotensinogen; ATM, ataxia telangiectasia mutated; ATR, ataxia telangiectasia and Rad3-related protein; BIRC5, baculoviral IAP repeat-containing protein 5; CDK, cyclin-dependent kinase; CTGF, connective tissue growth factor; ECM, extracellular matrix; FGF2, fibroblast growth factor 2; HR, homologous recombination; HSP27, heat shock protein 27; IL, interleukin; LIG4, DNA ligase 4; MDC1, mediator of DNA damage checkpoint protein 1; MRE11A, mitotic recombination 11A; NBN, nibrin; NHEJ, non-homologous end joining; NFKB1, nuclear factor-κB; OGG1, 8-oxoguanine DNA glycosylase; PRKDC, DNA-dependent protein kinase catalytic subunit; RB1, retinoblastoma 1; SOD, superoxide dismutase; TF, transcription factor; TGFB, transforming growth factor-β; TGFBR, TGFβ receptor; TNF, tumour necrosis factor; TP53BP1, TP53 binding protein 1; TP53INP1, tumour protein p53-inducible nuclear protein 1; VEGF, vascular endothelial growth factor ZYX, zyxin.