In vitro binding of 14C-misonidazole to hepatocytes and hepatoma cells

The binding rate of 14C-Misonidazole was determined for freshly isolated mouse hepatocytes, mouse hepatoma cells, EMT-6 tumor cells, and V79 Chinese hamster lung fibroblasts. At 10 microM drug concentration, the four different cell lines bound 14C-Misonidazole at rates of 12.4, 29.9, 51.6, and 13.5 pmoles/10(6) cells/hr, respectively. This relative order of binding was observed over a drug concentration range of 10-100 microM. These data indicate that in extreme hypoxia, mouse hepatocytes do not bind 14C-Misonidazole at a uniquely high rate in vitro, compared to other normal and tumor cell lines. This observation suggests that the increased binding to liver in vivo observed by other investigators is due to the liver existing at a reduced oxygen tension, compared to other normal tissues.