Abstract
The effect of radiation and cis-platinum in combination was studied in the intestinal crypt cell survival system of the LAF 1 mouse. The drug LD 50 60 was 22 mg/kg and the maximum tolerated dose (MTD) (LD 01) 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 D Q 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 B 6AF 1 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.
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