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The development and characterization of two types of chronic responses in irradiated mouse colon

Thesis/Dissertation ·
OSTI ID:6913478
The hypothesis to be tested is that there are two distinct types of chronic responses in irradiated normal tissues, each resulting from damage to different cell populations in the tissue. The first is a sequela of chronic epithelial depletion in which the tissue's integrity cannot be maintained. The other response is due to cell loss in the connective tissue and/or vascular stroma, i.e. a primary' chronic response. The purpose of this study was to test the hypothesis in the murine colon by first, establishing a model of each chronic response and then, by determining whether the responses differed in timing of expression, histology, and expression of specific collagen types. The model of late damage used was colonic obstructions/strictures induced by a single dose of 27 Gy ( consequential' response) and two equal doses of 14.75 Gy (t = 10 days) ( primary' response). Consequential' lesions appeared as early as 5 weeks after 27 Gy and were characterized by a deep mucosal ulceration and a thickened fibrotic serosa containing excessive accumulations of collagen types I and III. Both types were commingled in the scar at the base of the ulcer. Fibroblasts were synthesizing pro-collagen types I and III mRNA 10 weeks prior to measurable increases in collagen. A significant decrease in the ratio of collagen types I:III was associated with the consequential' response at 4-5 months post-irradiation. The primary' response, on the other hand, did not appear until 40 weeks after the split dose even though the total dose delivered was approximately the same as that for the consequential' response. The primary' response was characterized with an intact mucosa and a thickened fibrotic submucosa which contained excessive amounts of only collagen type I. An increased number of fibroblasts were synthesizing pro-collagen type I mRNA nearly 25 weeks before collage type I levels were increased.
Research Organization:
Texas Univ., Houston, TX (United States)
OSTI ID:
6913478
Country of Publication:
United States
Language:
English