Topographic variations in the clonogenic response of intestinal crypts to cytotoxic treatments

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Abstract
In the intestinal crypt microcolony assay, a surviving fraction of whole crypts is calculated conventionally by dividing the number of regenerating crypts 3-4 days after treatment by the number of crypts in untreated mice, both measured around a complete intestinal circumference in transverse sections of gut. The relation to the mesenteric attachment of the gut, crypts in different regions of the circumference differed in their survival characteristics after radiation or mechlorethamine hydrochloride (HN2). Crypts associated with Peyer''s patches were resistant to both agents (large initial shoulder, shallow slope). The mode of administration of NH2 (i.p. vs. i.v.) influenced the shape of the crypt survival curve. Differences in size of shoulder and slope affected the estimate of numbers of microcolony-forming cells per crypt (A). For radiation, this number varied 7-fold, depending on the region of circumference chosen for analysis. Different agents of assay resulted in radically different values for A.

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