Effect of .BETA.-adrenergic stimulants on cytotoxicity of mitomycin C in HeLa cells.

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Abstract
Effects of several autonomic agents on the cytotoxicity of mitomycin C in [human cervical carcinoma] HeLa cells were studied. When .beta.-adrenergic stimulants such as isoproterenol, epinephrine, terbutaline and turobuterol were added at concentrations over 10-14 M 15-60 min before mitomycin C, the colony-forming ability of HeLa cells was significantly inhibited more than by mitomycin C alone. The action of isoproterenol and epinephrine on the colony-forming ability of the cells was abolished by propranolol. The intracellular cAMP level of HeLa cells reached the peak of about 2-fold the basal level at 30 min after the addition of 10-8 M isoproterenol. In combination with mitomycin C, the high level of intracellular cAMP induced by isoproterenol was maintained for a significantly longer period in comparison with that by isoproterenol alone, while mitomycin C alone caused essentially no change in the cAMP level. The pretreatment with dibutyryl cAMP also enhanced the effect of mitomycin C. The synergistic effect of .beta.-adrenergic stimulants on the cytotoxicity of mitomycin C is evidently mediated via stimulation of the .beta.-adrenoceptors of HeLa cells which elevates the intracellular cAMP for a long time in combination with mitomycin C.