title: A study of the small intestine as a limiting normal tissue in radiotherapy
Creators: name: Hamlet, Roy
Publisher: name: University of Glasgow
Year: 1980

description: In clinical radiotherapy the dose to a tumour is limited, in any particular instance, to the dose which can be tolerated by the surrounding normal tissues. The experimental work described in this thesis deals with an investigation of one of these limiting normal tissues, the gut. The animal system chosen was also used to investigate some of the predictions of one of the mathematical models devised to estimate normal tissue tolerance in clinical situations. This was the CRE (Cumulative Radiation Effect) model. This thesis consists of seven chapters; the First Chapter contains a brief introduction, a description of the proposed research and a review of the background literature. The literature review is not totally comprehensive but was chosen to introduce data and information about the animal system used in the research, the experimental methods which were employed and the mathematical model investigated. The Second Chapter, entitled Materials and Methods, describes the experimental animals and the conditions in which they were housed; the irradiation and dosimetry procedures and the methods used for the preparation and examination of the tissue specimens removed from the irradiated and control animals. Chapter Three describes intestinal crypt survival and scanning electron microscopy of the mucosa of the small intestine after single whole body doses of neutron or gamma irradiation. The results obtained demonstrate that scanning electron miscroscopy of the surface mucosa of the intestine, although difficult to quantitate, is a much more sensitive indicator of intestinal damage at low dose levels than the more standard methods involving the enumeration of surviving crypts of Lieberkuhn in a section of intestine. Being a direct method of observation it is likely to be more accurate than the usual extrapolation from the exponential fall of crypt numbers after high doses of irradiation (ie, greater than 500 rads neutrons or 900 rads gamma rays). The results also demonstrate that the morphology of the mucosa follows a different pattern following neutron irradiation than the pattern seen after gamma irradiation. Chapter Pour contains a description of intestinal crypt survival and surface morphology after fractionated doses of X and gamma irradiation. The results show that there is a lack of correlation between the damage expressed in terms of either crypt survival or mucosal damage in two out of three fractionated schedules. These observations are discussed in terms of their relevance to therapy situations. The Fifth Chapter describes an investigation of the alternating fractionation formula of the CRE model. It can be seen that of the two major predictions of the formula only one is confirmed by the experimental results. There is a discussion of the possible reasons underlying these differences and similarities and an assessment of the formula in general use. Chapter Six contains a description of an investigation of the CRE formula which deals with the allowances that must be made when gaps occur in fractionated irradiation schedules. There is a comparison of the results with the predictions of the formula and a discussion of the factors which must be taken into account to try and overcome some of the shortcomings of the model. Chapter Seven is a summary of the conclusions drawn from the experimental research. It also contains a section dealing with possible further work suggested by the experimental results. The Appendices, which follow the conclusions chapter, contain descriptions of one of the irradiation facilities and some of the more important ancillary experiments.