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

Abstract

In the intestinal crypt microcolony assay, a "surviving fraction" of whole crypts is calculated conventionally by dividing the number of regenerating crypts three to four days after treatment by the number of crypts in untreated animals, both measured around a complete intestinal circumference in transverse sections of gut. We show that in relation to the mesenteric attachment of the gut, crypts in different regions of this circumference differ in their survival characteristics after radiation or mechlorethamine hydrochloride ("HN2"). Crypts associated with Peyer's patches are resistant to both agents (large initial shoulder, shallow slope). The mode of administration of HN2 (IP vs. IV) influences the shape of the crypt survival curve. Differences in size of shoulder and slope affect the estimate of numbers of microcolony-forming cells per crypt (A). For radiation, this number can vary sevenfold, depending on the region of circumference chosen for analysis. Different agents of assay result in radically different values for A.