Ronald F. Hagemann

Fasting and refeeding: cell kinetic response of jejunum, ileum and colon.

Following a period of fasting, feeding a normal diet results in a burst of DNA synthesis in the crypts of the colonic epithelium. This is due largely to a prompt entry of cells, blocked in G1, into S. Peak levels of S cellularity exceed 4 times the fasting, and 2 times the normal fed, control values. Refeeding a low residue diet (soluble casein, glucose and corn oil) results in a return to control levels of proliferative activity, but no hyperplasia.

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.

Response of the murine gastrointestinal epithelium to cis-dichlorodiammineplatinum II: Radiation combinations

Single doses of cis-dichlorodiammineplatinum II (cis DDP) up to 8 mg/kg produced a dose-dependent inhibition of proliferative activity with a subsequent period of compensatory hyperplasia in the colon. The stomach was less responsive to cis DDP. Cis DDP-radiation combinations produced a dimunition in the proliferative response of the colon when compared to that following radiation only. This response was only seen in the stomach following 8 mg/kg of cis DDP and radiation. Cytokinetic analysis of the jejunal response to 8 mg/kg of cis DDP showed a gradual reduction in LN and MF/crypt with a reduction in the rate of DNA synthesis of S-phase cells through 8 hours post-treatment. By 24 hours the cellular DNA synthetic rate had recovered, although the number of S-phase cells was further reduced. The previously reported jejunal response to cis DDP-radiation combinations involved a reduction in crypt survival, coupled with a reduced proliferative capacity of surviving cells. Further investigation has revealed a possible inhibition of radiation damage repair by cis DDP, leading to increased levels of cell kill with the combination and reduced recovery of DNA synthetic rates in surviving cells.

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.

An iron requirement for the synchronous progression of colonic cells following fasting and refeeding.

Evidence is presented to show dietary iron to be a major co‐factor in the colonic hyperplasia observed following fasting and refeeding. the iron component serves to remove a fasting induced colonic G1 cycle block and produce the resultant synchronous progression of cells through the cycle. Deleting iion from the refed diet results in no colonic hyperplasia and/or synchronous progression of cells. the results are discussed from the viewpoint of colonic steady state cell renewal and as a possible tool for the study of in vivo steady state cell renewal.

COMPENSATORY PROLIFERATIVE RESPONSE OF THE COLONIC EPITHELIUM TO MULTI-FRACTION IRRADIATION?

Abstract Colonic proliferation rate was measured during a 1 week period of fractionated radiation exposures, which totaled 1000 R/5 day week. The measurement period constituted either the first or the fourth week of continued therapy. In all cases, colonic cell production attained or exceeded control levels when considered over the 7 day span. This indicates that, in the colon, the principal determinant of acute radiation tolerance to fractionated therapy resides in this tissues ability to undergo pronounced compensatory hyperplasia following radiation damage. This capacity was found to be greater during the fourth week of therapy than during the first week, which indicates: (1) the importance of damage recognition in the initiation of the compensatory proliferative response and (2) the lack of high total dose radiation damage to proliferation control mechanisms per se .

Temporary localized depression of tritiated thymidine incorporation in mouse tissues after pulse labelling.

Approximately two to six in every 100 mice injected with 3H‐TdR appear not to incorporate the labelled precursor into the DNA. The tritium activity appears to be distributed throughout these poor utilizers of thymidine. The lack of incorporation of the precursor is not always general to the whole animal but may be restricted to a given tissue. The effect does not appear to be permanent but varies with time.

A NON‐DESTRUCTIVE METHOD FOR MEASURING INTESTINAL CELL TRANSIT TIME

Villous exfoliation of intestinal epithelial cells, which had been previously labeled in the crypt with 125I‐iododeoxy‐uridine, can be detected by thyroidal accumulation of the liberated 125I‐. The latter can be monitored externally. The interval between labeled precursor injection and the steep portion of the thyroid activity accumulation curve corresponds to the intestinal cell transit time, as measured by destructive techniques, in three animal species. The technique allows estimations of intestinal cell transit time to be made on an individual basis, and can be expeditiously applied to large animals. Very small tracer doses are required for detection.

Response of mouse Lewis lung carcinoma to variation in dietary retinyl esters

Abstract The effect of manipulating dietary concentrations of retinyl acetate or retinyl palmitate on the growth of subcutaneous murine Lewis lung carcinoma was studied. Both deficiencies and excesses of vitamin A resulted in slowed tumor growth. An optimal intermediate level of dietary vitamin A for solid tumor growth was established. Although previous studies have suggested that established subcutaneous Lewis tumors were responsive to various forms of chemotherapy, a significant increase in the efficacy of BGNU therapy was observed when drug treatment was coupled with either deficient or excessive amounts of dietary retinyl esters.