EFFECTS OF ADRIAMYCIN AND X-IRRADIATION ON THE MURINE DUODENUM

The effects of a single dose of X-irradiation at various times following a single dose of Adriamycin have been evaluated at the cellular level (duodenal crypt cell survival) and whole-animal level (LD 50 6; the dose required to kill 50% of the animals in 6 days). Qualitatively, the 10-clone doses (the X-ray dose required to reduce crypt survival to 10) parallel the data for the effects of Adriamycin on the rate of DNA synthesis. In contrast, changes in the slopes (Do) of the survival curves for the combined treatments do not correlate with the ADR-induced inhibition of DNA synthesis. The (LD 50 6 doses for the combined treatments also parallel the cellular toxicity data initially but for intervals from 2 to 14 days, when the cellular parameters are back to normal, there is still evidence for an Adriamycin-enhanced radiotoxicity. The discrepancy between the Adriamycin-enhanced duodenal cellular radiotoxicity and whole-body radiotoxicity is not surprising with a systemic drug like Adriamycin; however, neither the specific tissue(s) affected nor the specific underlying molecular and cellular mechanism(s) are evident in the studies to date. © 1979.