S. Lesher

A METHOD FOR QUANTITATION OF PROLIFERATIVE INTESTINAL MUCOSAL CELLS ON A WEIGHT BASIS: SOME VALUES FOR C57BL/6

A method for determining the number of intestinal mucosal crypts, S cells, and total proliferative cells, on a weight basis has been presented. The number of crypts was obtained (following injection of tritiated thymidine) by dividing the disintegrations per minute (dpm) per mg intestine by the dpm per crypt. Multiplication of the number of crypts per mg by the number of labeled cells per crypt (determined radioautographically) resulted in the number of S cells per mg intestine. Division of the number of S cells per mg by the fraction of proliferative cells in S (obtained by cell cycle analysis) resulted in the number of proliferative cells per mg intestine.

Intestinal Crypt Survival and Total and Per Crypt Levels of Proliferative Cellularity Following Irradiation: Fractionated X-Ray Exposures

The split-dose response of jejunal crypt survival has been measured for first exposures of 1000 or 600 R (1400 R total exposure). The curves obtained are analyzed in terms of repair of sublethal da...

Irradiation of the G.I. tract: compensatory response of stomach, jejunum and colon

Abstract Proliferative cellularity in the stomach, jejunum and colon was measured following irradiation with 200, 500 and 1,000 R. A depression in cellularity was observed in all three tissues reaching a nadir at about 24 hours after exposure. This was followed, in the jejunum and colon, by an exposure-dependent overshoot in cell proliferation which reached a peak at three to four days in the former and five days in the latter. In contrast, no appreciable overshoot in proliferative cellularity in the stomach was observed. At 24 hours after irradiation, an unusual dose-effect relationship for cellularity was noted, which, along with the compensatory responses described, may have radiotherapeutic implications.

A New Method for Measuring Intestinal Cell Transit Time

Summary Intestinal epithelial cell transit time (time for cells to migrate from the proliferative zone of the crypts to the extrusion zone of the villi) was measured using liquid scintillation counting techniques. Tritiated thymidine was injected into mice every 5 hr, and at intervals segments of small intestine were removed for radioassay. The graph of disintegrations per minute per milligram (wet weight) versus time demonstrated a linear ascending limb (caused by cells incorporating tritiated thymidine and moving up the villi) followed by a plateau (representing a steady state between cell proliferation in the crypt and extrusion at the tips of the villi). The intersect of the regression lines for these two components of the curve represents the cell transit time.

The Modification of Gastrointestinal Tolerance and Responses to Abdominal Irradiation by Chemotherapeutic Agents

Groups of male DBA/2 mice were irradiated with partial abdominal exposures of x radiation ranging from 100 to 1,600 rads. Concomitant with radiation exposure and at 1 or 4 hours prior to, and at 1, 6, 24, or 48 hours after irradiation, various chemotherapeutic agents were administered, i.e., methotrexate, Cytoxan, adriamycin and BCNU. The results suggest that excessive gastrointestinal toxicity may result if aggressive chemotherapy is closely spaced with radiation exposure for the treatment of abdominal neoplasms. However, adjustment of dose and time patterns based on the proliferative responses of the mucosa may circumvent such toxicity to a large extent.

Damage and recovery assessment of the mouse jejunum to abdominal X-ray and adriamycin treatment

The influence of adriamycin on the post-irradiation proliferative response of the mouse jejunum was examined. Doses of either 5 or 10 mg/kg of adriamycin administered immediately after abdominal irradiation reduced the LD50/7 days by 300-400 R. Neither dosage of the drug reduced the number of surviving crypts, as measured by the crypt isolation and microcolony techniques, for a given radiation exposure. However, both drug dosages reduced the amount of post-irradiation compensatory hyperplasia, as measured by 3H-thymidine incorporation.

INTESTINAL CRYPT SURVIVAL AND TOTAL AND PER CRYPT LEVELS OF PROLIFERATIVE CELLULARITY FOLLOWING IRRADIATION: AGE RESPONSE AND ANIMAL LETHALITY.

Hydroxyurea was employed as a synchronizing agent for proliferative intestinal crypt cells in vivo. The drug was found to kill in excess of 90% of S-phase cells, and to block the G1 to S transition...

Intestinal Crypt Survival and Total and Per Crypt Levels of Proliferative Cellularity Following Irradiation: Role of Crypt Cellularity

Mice were given whole-body exposures of 500 R, or abdomen-only exposures of 900 R. One or 4 days later, when crypt cellularity was either relatively low or high, respectively, a graded series of ex...