INTERACTION OF RADIATION AND CIS-DIAMMINEDICHLOROPLATINUM(II) IN INTESTINAL CRYPT CELLS

The effect of radiation and cis-platinum in combination was studied in the intestinal crypt cell survival system of the LAF1 mouse. The drug LD 50 60 was 22 mg/kg and the maximum tolerated dose (MTD) (LD01) was 13 mg/kg. That dose caused 80% cell kill when given either 3 hrs after or 2 hrs before a dose of 1100 rad. When the MTD was given from -48 to +48 hrs relative to a dose of 1110 rad, survival fluctuated with minima at -12 hrs, 0 and +12 hrs. A radiation survival curve determined 2 hrs after an MTD drug dose was parallel to the control, but shifted to lower doses due to cell kill. The extrapolated DQ was 280 rad, but the split dose survival ratio was only 1.3 compared to a control value of 7 at the same survival level. A repeat experiment with B6AF1 mice yielded a survival ratio of 3 vs 6 for controls. Cis-platinum may reduce repair of radiation injury, as well as kill intestinal crypt cells. © 1979.