The role of gene mutations and gene products in intestinal tissue reactions from ionising radiation

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• 作者：Jolyon H. Hendry^a ; ^{jhendry2002uk@yahoo.com} ; Kensuke Otsuka^b
• 关键词：Ascl2 ; achaete-scute family bHLH transcription factor 2 ; ASM ; ase acid sphingomyelinase ; ATM ; ataxia telangiectasia mutated ; Bak1 ; Bcl2 antagonist/killer 1 ; Bax ; Bcl2 associated X ; Bcl-2 ; B-cell lymphoma 2 ; bFGF ; basic fibroblast growth factor ; Bmi1 ; B lymphoma Mo-MLV insertion region 1 homolog ; BMP ; bone morphogenetic protein ; BMT ; bone marrow transplants ; CBC ; crypt base columnar ; DLL1 ; delta-like 1 ; DNA-PKcs ; DNA-dependent protein kinase catalytic subunit ; EGF ; epidermal growth factor ; FGF ; f
• 刊名：Mutation Research/Reviews in Mutation Research
• 出版年：2016
• 出版时间：October-December 2016
• 年：2016
• 卷：770
• 期：part_PB
• 页码：328-339
• 全文大小：1243 K
• 卷排序：770

文摘

The response of the intestine to (low linear-energy-transfer) ionising radiation is reviewed regarding the cellular basis to the reactions, the regenerative processes which restore the tissue, and external agents which aid its recovery. In the steady-state, it is generally considered that the crypt cell lineages in both small and large intestine are maintained by a small number of stem cells, but there are differences for example in the composition of their niche residence and in the numbers of transit cell generations. Various cell surface markers are now available to indentify particular lineage cell types. Radiation doses up to 1 Gy cause apoptotic stem-cell death in particular locations, at higher doses to >6 Gy Lgr5+ stem cells are required for normal intestinal recovery, and at >8 Gy some crypts are sterilised and the probability of animal death from intestinal injury increases with higher doses. Mutations in repair genes, tumour suppressor genes, and survival genes cause various degrees of stem cell and clonogenic cell radiosensitisation. Recent evidence is suggesting much plasticity in the crypt cell lineage, potentially contributing to flexibility in the hierarchical lineage, clonogen number variations and the sensitisation differences. Knockout mice for many different genes have been used to detect their role in both steady state and in irradiated conditions, expected to lead to further insight to the damage and restorative processes. Many different external agents have been used to ameliorate intestinal reactions, including prostaglandins, interleukins, angiogenic and epithelial growth factors, other cytokines, and intraluminal factors.