Proliferative Characteristics of Intestinal Stem Cells. Response and Protection to High Energy or Fission Spectrum Neutrons or Photons

摘要

Cytosine Arabinoside (Ara/C) is an s phase cytoxic agent. Since nearly half the proliferating cells in the murine crypt are in the S phase, Ara/c treatment, the clonogenic cells (the cells responsible for tissue regeneration) in the crypt are considerably less sensitive to photon radiation than colonogenic cells of control animals. Evidence suggests that the reason for this radioprotection by a toxic agent is the Ara/c-induced alteration in the cell age distribution of the clonogenic cells. Normally, the clonogenic cells are in a G sub 1 or G sub O stage of the cell cycle and are unaffected directly by Ara/c; however, following Ara/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 toi late S phase of the cell cycle where they are less sensitive. WR-2721 appears to protect cells from radiation throughout the cell cycle and most likely acts through a mechanism different the 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 combination was slightly better than each agent and there was no additional protection of Ara/c combined with WR-2721 for injury by JANUS fission spectrum neutrons. These treatments did not alter the animal response at doses in the bone marrow lethal range.