Evaluation of 2-(3-aminobenzamido)-2-deoxy-D-glucose as a radiosensitizer.

Abstract

3-Aminobenzamide (3-AB), an inhibitor of poly(adenosine diphosphate [ADP]-ribose) synthetase, functions as a radiosensitizer in several human tumor cell lines. 2-(3-AB)-2-deoxy-D-glucose (3-AB-G) was designed to increase preferentially the intracellular concentration of the drug in tumor cells. Both the toxicity and effectiveness of 3-AB-G as a radiosensitizer were determined. The toxicity of 3-AB-G was measured in HeLa and Chinese hamster ovary cells. The radiosensitizing effect of 3-AB-G was determined for both cell lines. 3-AB-G was not toxic to cells at concentrations of 10 mmol/L or less. 3-AB-G did not alter cell survival after irradiation. 3-AB-G was not an effective radiosensitizer for the cells tested. Coupling 2-deoxyglucose to 3-AB may block the uptake of the inhibitor into the cell by altering the ability of the receptor to recognize the molecule or may interfere with the specificity of the inhibitor for poly(ADP-ribose) synthetase.