EFFECT OF OXYGEN ON MISONIDAZOLE CHEMOSENSITIZATION AND CYTO-TOXICITY INVITRO

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (10) , 4409-4413
Abstract
In order to assess the effect of O2 on chemopotentiation by misonidazole (MISO), EMT-6/Ro tumor cells were exposed in vitro to combinations of CCNU [1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea] and 1.0 mM MISO in culture medium equilibrated at various O2 concentrations. The effect of O2 on MISO cytotoxicity was similarly determined and compared with the relationship obtained for chemosensitization. MISO cytotoxicity and chemopotentiation were both O2 sensitive, being maximal under anoxic conditions. The pattern of O2 sensitivity was virtually identical for the 2 activities. A similar metabolic pathway, i.e., the O2-sensitive reduction of MISO to the nitroradical anion by cellular nitroreductases, apparently is involved in the mechanism of both activities. Chemopotentiation can be expressed in cells treated at intermediate O2 tensions. The implications of these findings with respect to the magnitude of chemopotentiation in vivo and the enhancement of normal tissue damage in animals treated with MISO and chemotherapy agents is discussed.