Chemotherapeutic drugs as indirect oxygen radiosensitizer.

We have characterized the oxygen distribution in V-79 spheroids which were grown by the spinner flask method. Using ultramicroelectrodes with tip diameters of 1-5 microns and a perfusion system whereby the spheroids' milieu could be maintained and controlled, we found plateau pO2 values of less than 10 mm Hg in spheroids of greater than 500 microns in diameter. Data from experiments using respiration inhibitory drugs indicate that the characteristics of the outer layers of cells is the major determinant of the oxygen profile in the interior. Parallel control radiobiological experiments confirmed the control pO2 measurements, and formed the basis for the experiments using the potential indirect radiation sensitizers: Chlorambucil and Mustargen.