Differential Radiosensitization of Human Tumour Cells by 3-aminobenzamide and Benzamide: Inhibitors of Poly(ADP-ribosylation)

Summary

The effect of 3-aminobenzamide (3AB) and benzamide (BZ) (inhibitors of poly(ADP-ribose) synthetase) on radiosensitivity was investigated in normal human fibroblasts and three human cell lines established from tumours with varying degrees of clinical radiocurability. The human tumour cell lines selected were: (1) Ewing's sarcoma, a bone tumour usually considered radiocurable with moderate radiation doses; (2) lung adenocarcinoma, a tumour considered radiocurable with high doses of radiotherapy; and (3) osteosarcoma, a very resistant tumour which is rarely controlled by standard doses of radiotherapy. Poly(ADP-ribose) synthetase inhibitors were added to cultures 2h prior to irradiation and removed 24h after. Inhibitors were used at doses producing little or no toxicity in cells.

In the presence of these inhibitors, a differential radiosensitization was observed. Ewing's sarcoma cells and normal human fibroblasts were sensitized to an equal extent by either 8 mm 3AB or 4 mm BZ. However, no sensitization was observed at these concentrations in the lung adenocarcinoma cells or osteosarcoma cells. The degree of radiosensitization in vitro by 3AB and BZ correlates well with the clinical radiocurability of these tumours in vivo.

• poly(ADP-ribosylation)
• tumour cells
• 3-aminobenzamide
• benzamide