Document Details


Title:
THE PROLIFERATIVE CHARACTERISTICS OF INTESTINAL STEM CELLS, RESPONSE AND PROTECTION TO HIGH ENERGY OR FISSION SPECTRUM NEUTRONS OR PHOTONS
Author(s):
Addressee:
MEHAS T C
Document Location:
Location - NNSA/NSO Nuclear Testing Archive Address - P.O. Box 98521 City - Las Vegas State - NV Zip - 89193-8521 Phone - (702)794-5106 Fax - (702)862-4240 Email - CIC@NV.DOE.GOV
Document Type:
REPORT
Publication Date:
1986 Apr 30
Declassification Status:
Never classified
Document Pages:
0032
Accession Number:
NV0051265
Document Number(s):
DNATR86155
OpenNet Entry Date:
1994 Aug 26
Description/Abstract:
CYTOSINE ARABINOSIDE (ARA/C) IS AN S PHASE CYTOTOXIC AGENT. SINCE NEAR LY HALF THE PROLIFERATING CELLS IN THE MURINE CRYPT ARE IN THE S PHASE , ARA/C KILLS 50 PERCENT OF THIS CELL POPULATION. HOWEVER, 12 HOURS AF TER ARA/C TREATMENT, THE CLONOGENIC CELLS (THE CELLS RESPONSIBLE FOR T ISSUE REGENERATION) IN THE CRYPT ARE CONSIDERABLY LESS SENSITIVE TO PH OTON RADIATION THAN CLONOGENIC CELLS OF CONTROL ANIMALS. EVIDENCE SUGG ESTS THAT THE REASON FOR THIS RADIOPROTECTION BY A TOXIC AGENT IS THE ARA/C-INDUCED ALTERATION IN THE CELL AGE DISTRIBUTION OF THE CLONOGENI C CELLS. NORMALLY, THE CLONOGENIC CELLS ARE IN A G OR GO STAGE OF THE CELL CYCLE AND ARE UNAFFECTED DIRECTLY BY ARA/C; HOWEVER, FOLLOWING AR A/C TREATMENT OF AN ANIMAL, THE CLONOGENIC CELLS ENTER THE CELL CYCLE. BY 12 HOURS, THE CLONOGENIC CELLS PROCEED IN A PARTIALLY SYNCHRONIZED FASHION TO A MID TO LATE S PHASE OF THE CELL CYCLE WHERE THEY ARE LES S SENSITIVE. WR-2721 APPEARS TO PROTECT CELLS FROM RADIATION THROUGHOU T THE CELL CYCLE AND MOST LIKELY ACTS THROUGH A MECHANISM DIFFERENT TH AN ARA/C. RESULTS OF THIS CONTRAST SHOWED THAT THE COMBINATION OF ARA/ C AND WR-2721 PROTECTED THE GUT FROM PHOTON INJURY TO A GREATER EXTENT THAN EACH AGENT ALONE. THE PROTECTION FROM FERMILAB NEUTRONS BY THE C OMBINATION WAS SLIGHTLY BETTER THAN EACH AGENT AND THERE WAS NO ADDITI ONAL PROTECTION OF ARA/C COMBINED WITH WR-2721 FOR INJURY BY JANUS FIS SION SPECTRUM NEUTRONS. THESE TREATMENTS DID NOT ALTER THE ANIMAL RESP ONSE AT DOSES IN THE BONE MARROW LETHAL RANGE. THESE DATA ARE CONSISTE NT WITH FINDINGS THAT THE INTESTINAL CLONOGENIC CELL AGE DISTRIBUTION HAS LESS EFFECT ON HIGH LET RADIOSENSITIVITY. THE RESULTS OF EXPERIMEN TS FUNDED BY THIS CONTRACT SHOW THAT THE INTESTINAL STEM CELLS ARE NOR MALLY IN A GO STAGE OF THE CELL CYCLE AND RESPOND TO ARA/C BY ENTERING THE CELL CYCLE AT THE S PHASE IN WHICH THEY SHOW A PRONOUNCED CHANGE IN RADIOSENSITIVITY TO PHOTON INJURY. THESE STUDIES ARE PART OF THE OV ERALL GOAL TO RESEARCH MECHANISMS OF INTESTINAL PROTECTION FROM PHOTON AND NEUTRON INJURY.


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