A SYSTEM FOR DETERMINING THE PHARMACOLOGY OF INDIRECT RADIATION SENSITIZER DRUGS ON MULTICELLULAR SPHEROIDS

Abstract

The physiological of multicellular spheroids of different sizes grown from Chinese hamster lung fibroblast (V79) cells was characterized. O2 tension distributions within the spheroid was studied. This was achieved using ultramicroelectrodes with tip diameters of 1-5 .mu. and a perfusion system whereby environmental conditions such as flow, temperature and chemical makeup of the milieu could be measured and controlled. Plateau PO2 [partial pressure of O2] values of < 10 mm Hg were consistently obtained from spheroids under various conditions. These distributions were modified by indirect radiation sensitizer drugs such as mechlorethamine HCl (mustargen) at nontoxic doses. Determinations of the inhibitory capacities of [mechlorethamine hydrochloride, mustargen and bacitracin] on the respiration rate of constituent cells of multicellular spheroids in single-cell suspensions were made. Apparently, there are hypoxic cells in spheroids whose radioresistance may be modified by essentially nontoxic levels of indirect radiosensitizer drugs and the system described shows great promise for screening agents which may modify radiation response.