Changes in ultrastructure and function of hypoxic V79 fibroblast cells after treatment with misonidazole

Abstract

Morphologic and enzymatic changes due to exposure to the radiosensitizing chemical, misonidazole, have been identified in V79 cells grown in a system in which oxygen tensions and culture density have been controlled. Misonidazole prevented the increase in mitochondrial size normally seen during exposure of these cells to conditions of moderate hypoxia (2 × 103 ppm O2). Mitochondrial size was also significantly decreased in cells from exponential cultures exposed to 1 mmol/1 misonidazole. Morphologic changes to the mitochondria that varied from data reported elsewhere were also noted. Misonidazole caused a significant initial decrease in cytochrome oxidase activity after 4 hours of exposure of aerobic and moderately hypoxic cultures that did not return to normal in chronically hypoxic cells during continued exposure to the drug.

Direct Effects of the Hypoxic Cell Sensitizer Misonidazole on Colony Formation in a Human Tumor Cloning Assay

“…Up to the moment it has not been possible to adequately determine the nature of direct MISO cytotoxicity under aerobic conditions. A variety of mechanisms had been suggested such as damage of cellular DNA (25), or involvement of mitochondrial energy pro¬ cesses with consecutive metabolic cell death (26,27). The results of our study certainly do not allow a conclusive statement in this regards.…”