Effect of misonidazole and low‐oxygen treatment on mouse tumors

Abstract

AbstractThe tumor cytotoxic activity of a bioreductive agent is dependent on the extent of tumor hypoxia. It is to be expected, therefore, that the tumor cytotoxicity of misonidazole will vary depending on whether it was administered to mice exposed only to an air‐breathing environment or whether it was administered either before mice were treated with 8% oxygen for 48 hr (maximal tumor levels of the drug will then coincide with an increase in tumor hypoxia) or after mice completed a 48‐hr 8% oxygen treatment (maximal tumor levels of the drug will now coincide with a reduction in the tumor hypoxic fraction). This was investigated using the 3‐methylcholanthrene‐induced rhabdomyosarcoma in BALB/c mice, the Fib/T tumor in WHT mice, and the CaNT tumor in CBA mice. The response of all three tumor types to the various treatments was determined by assessing post‐treatment tumor growth. An excision and in vitro colony‐forming assay was also used to assess Fib/T tumor response. Results indicated that only the 3‐methylcholanthrene‐induced rhabdomyosarcoma responded to misonidazole and only when the 48‐hr 8% oxygen exposure preceded drug administation. In explaining this result, it is proposed that misonidazole increases reperfusion damage that occurs when animals are returned to an air‐breathing environment following a low‐oxygen exposure. © Wiley‐Liss, Inc.