The interaction of radiation and bleomycin in intestinal crypt cells

Abstract

Using the intestinal crypt cell system, the effects of bleomycin (BLM) with radiation have been determined. The LD 50 60 in LAF, mice used was 167 units/kg and the MTD (LD 01) was 100 units/kg. Survival of crypt cells was reduced to 40% of radiation alone when drug was given 3 hr after a dose of 1100 rad, but to less than 1% when the drug was given 2 hr before. When maximum tolerated doses (MTD) were given from −48 to +48 hr relative to a dose of 843 rad, the combination was much more effective when drug was given from −12 to −2 hr before irradiation, survival dropping from 100 to 5 cells per circumference. This increased cell kill could be due to synchrony, interference with repair of BLM damage, or other factors. A radiation survival curve determined 2 hr after drug administration had a slope similar to controls, but was shifted toward lower doses. The extrapolated D q was 0 rad. A 3 hr split dose experiment yielded survival ratios of 6 for controls and 2 for mice given the MTD 2 hr before irradiation. There appears to be a marked interaction of bleomycin and radiation, with possible inhibition of repair of the radiation damage by bleomycin and possible inhibition of repair of the bleomycin damage by radiation.