Radiosensitization by diamide at low radiation doses.

In vitro studies in this laboratory indicated that at low radiation doses (0-3 Gy), sensitization by misonidazole diminishes. We have suggested that this results from a failure of misonidazole to enhance effectively the single-hit or alpha component of cell inactivation. Our low dose assay uses a partially automated microscopic analysis procedure which scores both surviving and killed cells. If enough cells are scored, this assay provides much better accuracy at low doses than the conventional assay. Recently, we have applied our low dose assay to a study of sensitization by diamide. This was done, in part, as a test of our assay system, since many investigators have shown that diamide substantially reduces the shoulder of the hypoxic cell survival curve. At high doses (D = 6.5 to 10 Gy, S = 0.1 to 0.01) we obtained for 150 microM diamide an enhancement ratio (ER) of 2.6 for hypoxic cells and 1.1 for aerobic cells. At low doses, 0-2.5 Gy, diamide still sensitized hypoxic cells well; with 150 microM diamide, the ER at 1 Gy (S = 0.8) was 2.0, about equal to the oxygen enhancement ratio (OER) at this dose. The fact that diamide shows good sensitization at low doses with our assay adds to the credibility of the assay and reduces the likelihood that our observations with misonidazole are an artifact of our system.