A quantitative histometric murine in vivo model of radiation-induced oral mucositis.
AffiliationCRC Epithelial Biology Group, UK.
MetadataShow full item record
AbstractGastrointestinal toxicity is a limiting factor in the effectiveness of cancer therapy. This toxicity is most visible in the mouth. There is considerable interest in developing strategies involving growth-factor manipulation of the epithelial stem cells to afford protection to these cells during treatment and/or to speed up the regenerative process following treatment. In order for this to be achieved, studies have to be undertaken in animal systems to demonstrate the proof of principle and determine optimal protocols. Here, a murine model for oral mucositis based on measurements of tissue cellularity at various times after exposure to radiation was used to investigate cytotoxicity. Several sites in the mouth were analysed and the pronounced circadian rhythm in these various epithelial sites determined. The circadian rhythm is important in that it would determine the timing of administration of growth factors. A microscope with an interactive computer was used to define areas of epithelium and lengths of basal layer, within which, and along which, the total number of cell nuclei was determined over a range of times following exposure to 10, 20 and 30 Gy of X-rays. For various practical reasons, the ventral surface of the tongue was identified as the most appropriate tissue to analyse. Here, measurements of cellularity reached minimum values between 6 and 8 days following 20 Gy. Labelling of S-phase cells demonstrated foci of regeneration and a burst of proliferative regeneration that commenced at about 5 days and reached peak values at 8 days after irradiation. This burst of regenerative proliferation was coincident with the minimum in tissue cellularity on about day 8. The lower dose of radiation (10 Gy) had minimal effects on cellularity: after the higher dose (30 Gy), there was clearly a more severe level of cellular depletion. This quantitative model of oral mucositis could be used to study the effects of other cytotoxics, including combinations of agents, and the potential role of growth factors to reduce the severity of the cellular depletion and to speed up the kinetics of regeneration.
CitationA quantitative histometric murine in vivo model of radiation-induced oral mucositis. 1998, 43 (7):567-77 Arch. Oral Biol.
JournalArchives of Oral Biology
- Cell kinetic studies in the murine ventral tongue epithelium: mucositis induced by radiation and its protection by pretreatment with keratinocyte growth factor (KGF).
- Authors: Potten CS, Booth D, Cragg NJ, Tudor GL, O'Shea JA, Booth C, Meineke FA, Barthel D, Loeffler M
- Issue date: 2002 Aug
- Proliferation equivalent of 'accelerated repopulation' in mouse oral mucosa.
- Authors: Dörr W, Emmendörfer H, Haide E, Kummermehr J
- Issue date: 1994 Aug
- Protective effects of systemic dermatan sulfate treatment in a preclinical model of radiation-induced oral mucositis.
- Authors: Gruber S, Frings K, Kuess P, Dörr W
- Issue date: 2018 Jul
- Effect of selective inhibitors of inflammation on oral mucositis: preclinical studies.
- Authors: Haagen J, Krohn H, Röllig S, Schmidt M, Wolfram K, Dörr W
- Issue date: 2009 Sep
- Changes in the effect of dose fractionation during daily fractionated irradiation: studies in mouse oral mucosa.
- Authors: Pabst S, Spekl K, Dörr W
- Issue date: 2004 Feb 1