THE EFFECT OF A SINGLE INJECTION OF HYDROXYUREA ON CELL POPULATION KINETICS IN THE SMALL BOWEL MUCOSA OF THE RAT

Abstract

The effect of a single injection of the antitumor agent hydroxyurea (HU) on cell population kinetics in the jejunal crypt of the rat was studied using autoradiography with 3H-thymidine and metaphase arrest with vincristine. HU appeared to act selectively on cells in the S phase producing inhibition of DNA synthesis and cell death. The deficit in proliferating cells was made good by a decrease in cell cycle time and an increase in growth fraction. Particular attention was paid to the basal, slowly cycling (and possibly clonogenic) crypt cells. Early in the recovery sequence an increase in cell production rate was found in the base of the crypt. Basal crypt cells, having survived cycle-specific insult because of long cell cycle times, probably proceed to repopulate the depleted proliferative compartment.