TIME-DEPENDENCE OF INTESTINAL PROLIFERATIVE CELL RISK VS STEM-CELL RISK TO RADIATION OR COLCEMID CYTO-TOXICITY FOLLOWING HYDROXYUREA

A comparison of the time dependence between intestinal crypt damage by hydroxyurea (HU) and crypt cell or clonogenic cell risk to colcemid (COL) cytotoxicity was made to determine if rapidly cycling cells are clonogenic or if crypt damage by HU induces clonogenic cells into rapid cycle. B6CF1/An1 mice were given 15 mg HU 15 min before or after increments of 137Csγ-irradiation for the crypt colony assay. HU reduced the crypt cells from 254 ± 11 to 170 ± 8; however, the clonogenic cell survival curve was unaltered. At 2 hours after administration of HU, the dose for clonogenic cell survival giving rise to 10 microcolenies/circumference was reduced from 1625 rad in controls to 1375 rad; but at 6 hours after HU, the dose was 2200 rad. Hydroxyurea appears to stimulate stem cells from G, into rapid cycle. To test this, groups of mice were given HU and at 6, 12, 18, 24, and 30 hr, a 12 hr treatment of COL was given to kill cells in M phase of the cell cycle. At 3 hr after the last COL injection, mice were killed for crypt cell counts or given 1100 rad 137Csγ for the microcolony assay. The greatest clonogenic cell risk ( 38 40) occurred when COL was begun 12 hr after HU, but the greatest total crypt cell risk (183/254) occurred when COL was begun 24 hr after HU at a time when clonogenic cell risk was 10/40. The data suggest that the cell cycle kinetics of clonogenic and rapidly proliferating cells are different. Further, damage to crypts by HU stimulates G, clonogenic cells into rapid cycle. © 1979.