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Cytosar-U (Ara-C) induced changes in mouse jejunal crypt epithelial kinetics and radiosensitivity to gamma rays and fast neutrons

Journal Article · · Int. J. Radiat. Oncol., Biol. Phys.; (United States)
Pretreatment with the S phase specific cytotoxic agent Cytosine Arabinoside (Ara-C) protects the intestinal stem cells from gamma radiation injury by nearly tenfold. Studies were undertaken to test whether an altered cell age distribution could account for the reported duration and degree of Ara-C induced protection and to measure the degree of protection form the high energy neutrons of the Fermilab Cancer Treatment Facility. The number of regenerating microcolonies per jekima; corci,feremce om Ara-C treated and irradiated animals was compared to irradiated controls. Another group of mice were fiven Ara-C but in the 12-hour interval between Ara-C and irradiation, colcemid was given every 3 hours to continuously block and kill cells in mitosis. The results suggest that Ara-C given 12 hours prior to neutron irradiation protects intestinal stem cells to nearly the same degree as it does from /sup 137/Cs gamma-ray damage. Furthermore, the control split-dose recovery ratio to neutron irradiation at 1,2, or 3 hours was 1.8 and was unchanged 12 hours after Ara-C. Colcemid reduced the crypt cell population to less than half the normal 250 cells per crypt; however, the cell survival curve was unaltered from the survival curve 12 hours after Ara-C. These results suggest that Ara-C recruits intestinal clonogenic stem cells, but inhibits their normal passage through DNA synthesis.
Research Organization:
Rush Univ. Presbyterian-St. Luke's Medical Center, Chicago, IL
OSTI ID:
5514258
Journal Information:
Int. J. Radiat. Oncol., Biol. Phys.; (United States), Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States) Vol. 9:4; ISSN IOBPD
Country of Publication:
United States
Language:
English