Role of carcinogenesis related mechanisms in cataractogenesis and its implications for ionizing radiation cataractogenesis

Article ID	Journal	Published Year	Pages	File Type
10899412	Cancer Letters	2015	13 Pages	PDF

Abstract

Ionizing radiation is a proven human carcinogen and cataractogen. The crystalline lens of the eye is among the most radiosensitive tissues in the body. A clouding of the normally transparent lens (i.e., cataract) is very common. Conversely, the lens continues to grow throughout life without developing tumors, suggesting that the lens possesses strong anti-carcinogenesis mechanisms. There is mounting evidence that mutations of oncogenes, tumor suppressor genes, DNA repair genes involved in base excision repair, nucleotide excision repair, and DNA double-strand break repair, and genes involved in intercellular interactions (e.g., via connexin gap junctions), and inflammation affect cataract development. Associations of these factors with cancer have long been recognized, highlighting that cataractogenesis shares some common mechanisms with carcinogenesis. This paper briefly overviews the current knowledge on the potential involvement of tumor related factors, DNA repair factors, intercellular interactions and inflammation in spontaneous cataractogenesis, and discusses its implications for cataractogenesis induced by targeted and nontargeted effects of ionizing irradiation.

Keywords

Sirt1 STAT3 PI3K DSB CNV GST COX-2 NHEJ FGF RTS VIC PSC MCP-1 MMP-2 RNS BER Hsp GSTM1 GJIC BLM Pax6 LFC RFC cKO AQP NBN LLR NDRG2 N-myc downstream regulated gene 2 Brg1 NTE IFI27 ARF NF2 LEC γH2AX HPV16 EphA2 SV40 ssDNA RPA TGFβ1 regulated upon activation normal T-cell expressed and secreted E2F1 SSB GSTP1 GSTT1 ICRP OGG1 CSB LTCC paired box gene 6 ERCC6 ACVR1 XPD DNA-PKcs APE1 HMGA1 6-4PP XPC TFIIH XRCC1 CSF2 NEIL1 WRN BubR1 CtIP INK4A Xeroderma pigmentosum complementation group C NBS1 FEN1 Human papilloma virus type 16 XLF DNA ligase I PCNA SCLU Hsf4 SWItch/Sucrose NonFermentable transcription factor II H Rothmund–Thomson syndrome NCOA6 XRCC4-like factor MgrB LIG1 (6-4) photoproduct 8-oxoguanine glycosylase 1 apurinic/apyrimidinic apurinic/apyrimidinic endonuclease 1 ataxia telangiectasia mutated BRCA1/2 c-Maf Single-stranded DNA DNA polymerase β NER Mϕ Polβ ROS SWI/SNF Proliferating Cell Nuclear Antigen aquaporin LET gap junctional intercellular communication inflammation Linear Energy Transfer CSA interleukin ionizing radiation Transforming growth factor β1 nucleotide excision repair base excision repair replication protein A copy number variation tumor necrosis factor α ATM CNS retinoblastoma Tumor suppressors Lens epithelial cell Lens fiber cell Bloom syndrome Nijmegen breakage syndrome 1 Werner syndrome central nervous system cyclooxygenase 2 DNA double-strand break DNA single-strand break conditional knockout Replication factor C E2F transcription factor 1 Fas Ligand FasL gap junction fibroblast growth factor TNF-α phosphatase and tensin homolog Phosphatidyl Inositol 3-kinase Flap endonuclease 1 Alternative reading frame TRAIL Crystalline lens tumor necrosis factor-related apoptosis-inducing ligand matrix metalloproteinase 2 Macrophage signal transducer and activator of transcription 3 RANTES knockout Homologous recombination ultraviolet light neurofibromin 2 Nibrin phosphorylated histone H2AX DNA-dependent protein kinase catalytic subunit Simian virus 40 monocyte chemoattractant protein 1 Heat shock protein Nonhomologous end joining Pten Brahma-related gene 1 L-type calcium channel crystallins International Commission on Radiological Protection connexin Cry glutathione S-transferase reactive nitrogen species Reactive oxygen species