Enhancement of the radiosensitivity of two human tumour cell lines by hexamethylene bisacetamide

The effect of the maturation-inducing polar solvent, hexamethylene bisacetamide (HMBA), on the radiosensitivity of two human tumour cell lines (clone A, a colon carcinoma; and EJ, a bladder carcinoma) was investigated. Exposure of clone A or EJ cells to HMBA resulted in a concentration-dependent increase in doubling time, a decreased plating efficiency and changes in cell morphology, which are consistent with the formation of a better-differentiated phenotype. Growth of clone A cells in 2 or 3 mM HMBA, followed by irradiation and plating into HMBA-free medium, resulted in a significant enhancement in radiosensitivity, as determined by colony-forming ability. A similar increase in radiosensitivity was detected for EJ cells; however, for these cells a concentration of 7 mM HMBA was required. The increased radiosensitivity caused by HMBA was observed primarily in the low-dose, shoulder region of the gamma-ray cell survival curves for both cell lines, which is reflected by an increase in the alpha component of the survival curve with essentially no effect on beta. These data indicate that HMBA can radiosensitise human tumour cells at concentrations and for exposure periods that can be achieved in the clinic.