The effect of the hypoxic cell drug SR-4233 alone or combined with the ionizing radiations on two human tumor cell lines having different radiosensitivity.

Abstract

The influence of the hypoxic cell drug, SR-4233, alone and/or combined with ionizing radiations on the survival of two human cell lines having very different intrinsic radiosensitivity was analysed. The killing effect of SR-4233 in hypoxia was similar for both cell lines. Twenty microM SR-4233 under hypoxic conditions had a killing effect equivalent to 6.6 Gy for the poorly sensitive cell line (HT29) and equivalent to 3.9 Gy for the highly sensitive cell line (SW48). The effect of SR-4233 and ionizing radiations on these two cell lines was tested in vitro: the cells were incubated for one hour in hypoxia with or without 20 microM SR-4233 and then irradiated in air. The HT29 cells that survived treatment with SR-4233 are more radiosensitive than untreated cells. However, their radiosensitivity is similar to that of cells that have been given a dose of 6.6 Gy. This suggests that SR-4233 acts additively, rather than as a radiosensitiser. As SR-4233 acts selectively in hypoxia, these results appear encouraging for the treatment of poorly-radiosensitive human tumors.