Non-nitro hypoxic cell radiosensitizers: Benzamide analogs

Benzamide compounds such as 3-aminoben-zamide (3-AB) which are potent inhibitors of the chromosomal enzyme poly (ADP-ribose) polymerase (ADPRP) have been shown to inhibit the repair of X-ray induced potentially lethal damage (PLD). Recently, the authors found that the benzamide analogs SR 4267 and SR 4284 are more potent inhibitors of ADPRP than 3AB (as determined by inhibition of /sup 3/H-NAD incorporation into the acid insoluble fraction of permeabilized CHO-To cells). In additional experiments CHO-HA-1 cells were exposed to varying concentrations (1-10 mM) of these compounds for 1 hr prior to irradiation under either aerobic or hypoxic conditions. The compounds were removed immediately after irradiation. The concentration of compound required to achieve a sensitizer enhancement ratio of 1.6 was 1-2 mM for both SR 4267 and SR 4284, which is comparable to that obtained with the electron-affinic radiosensitizer misonidazole