ENHANCEMENT OF TUMOR-CELL KILLING IN-VITRO BY PREIRRADATION AND POSTIRRADIATION EXPOSURE TO ACLACINOMYCIN-A

Aclacinomycin A (ACM), a potent inducer of leukemic cell differentiati on, significantly enhances the radiosensitivity of a human colon tumor cell line (Clone A) when cultures are exposed to 15-nM concentrations for 3 days before irradiation. We now demonstrate that incubation wit h ACM after irradiation can also enhance Clone A cell killing. The max imum increase in cell killing, based on colony-forming ability, occurr ed when Clone A cells were exposed for 1 h to 5 muM ACM added 1 or 2 h after irradiation. The post-irradiation ACM protocol reduced the term inal slope (as reflected by D0) of the radiation cell survival curve w ith no change in the low-dose, shoulder region of the curve (D(q) valu e). In contrast, for pre-irradiation treatment with ACM (15 nM, 3 days ), the shoulder region of the curve was reduced with no change in the terminal slope. For pre- and post-irradiation ACM treatment the dose e nhancement factors at 0.10 survival were 1.22 and 1.28, respectively. When ACM was given both before and after irradiation both the shoulder and terminal slope values decreased to produce a dose enhancement fac tor at a surviving fraction of 0.10 of 1.50. These data suggest that t he enhanced cell killing produced by pre- and post-irradiation treatme nt with ACM is achieved through different mechanisms.