Neutron and X-ray effects on small intestine summarized by using a mathematical model or paradigm

Abstract

The responses of intestinal tissues to ionizing radiation can be described by comparing irradiated cell populations qualitatively or quantitatively with corresponding controls. This paper describes quantitative data obtained from resin-embedded sections of neutron-irradiated mouse small intestine at different times after treatment. Information is collected by counting cells or structures present per complete circumference. The data are assessed by using standard statistical tests, which show that early mitotic arrest precedes changes in goblet, absorptive, endocrine and stromal cells and a decrease in crypt numbers. The data can also produce ratios of irradiated: control figures for cells or structural elements. These ratios, along with tissue area measurements, can be used to summarize the structural damage as a composite graph and table, including a total figure, known as the Morphological Index. This is used to quantify the temporal response of the wall as a whole and to compare the effects of different qualities of radiation, here X-ray and cyclotron-produced neutron radiations. It is possible that such analysis can be used predictively along with other reference data to identify the treatment, dose and time required to produce observed tissue damage.

Variations in Cell and Structure Populations along the Length of Murine Small Intestine

“…All features from the four tissue types were examined. The small intestine contains a functionally heterogeneous collection of cells and structures which all have been shown to respond in different ways to experimental challenge [Goodlad et al, 1990;Carr et al, 1991;Ettarh and Carr, 1996]. It is important therefore when establishing baselines for a multicellular organ that a holistic approach is employed and all cells and structures are investigated.…”

“…In addition to the counts, measurements of epithelium, connective tissues, muscle and nerve areas were made for each animal [Carr et al, 1991[Carr et al, , 1992a[Carr et al, , b, 1994a. Images of the section were captured using a Leitz Dialux 22 microscope with an attached video unit along with an image grabbing package running on a Macintosh CX II computer.…”

“…For the first part of the quantitative examination, using the technique of Carr et al [1991], profiles of the following cells and structures were counted per circumference: (A) villi: only full length attached villi continuous with the submucosal part of the section, (B) crypts: only those crypts containing 10 cells, excluding the Paneth cells, were counted (the rational for this is described elsewhere [Withers and Elkind, 1970;Potten and Hendry, 1985]; their bases were in close apposition to the muscularis externa, (C) enterocytes: the number of enterocytes per villi was counted for three randomly chosen villi meeting the criteria set in (A); this number was then averaged out over the three villi and then multiplied by the number of villi counted in that section, (D) globlet cells: total counts were obtained per circumference section on both the cryptal and villous goblet cell population, (E) endocrine cells: counts were carried per circumference section on the endocrine cell population within the crypt; these were distinguished from other cell types by their clear cytoplasm, their tear drop shape and the luminal direction of their apex, (F) Paneth cells: all the Paneth cells within the section were counted, (G) villous stromal cells: the number of nuclei present within the stromal core of the villus, meeting the criteria set in (A), were counted for three villi; these consisted of endothelial cells, muscles and fibroblasts, together with transitory cells such as lymphocytes, eosinophils, macrophages and mast cells; the mean was then multiplied by the number of villi in the section, (H) submucosal arterioles: all the submucosal arterioles were counted per circumference section, (I) muscle nuclei: all nuclei present per circumference section within the inner circular and the outer longitudinal layer were counted, (J) nerve plexus profiles: the number of myenteric (Auerbach) and submucosal (Meissner) nerve plexus profiles were counted within the section; each myenteric nerve plexus profile was counted separately when muscle tissue was present between them, and (K) mitotic figures: only those mitotic figures present within the crypt were counted per circumference section.…”

“…These parameters include, among others, stromal cells, apoptotic bodies, intra-epithelial lymphocytes, nerve plexus profiles and muscle nuclei. A number of these structures/cells have been shown to be affected by pathological conditions [Brandtzaeg et al, 1992;D'Inca et al, 1995], pharmaceutical challenge [Ettarh and Carr, 1996], immunological status [Ferguson, 1994], diet [Goodlad et al, 1990] and radiation challenge [Carr et al, 1991]. It is therefore important to have baseline data on all these parameters.…”

“…The first part of the quantitative data for this work was obtained by a technique already applied to assess changes following experimental irradiation [Carr et al, 1991[Carr et al, , 1992a[Carr et al, ,b, 1994a. This examines area measurements of epithelium, connective tissue, muscle and nerve, and documents 13 structural elements within these four main tissues.…”