Nicotinamide has been shown to sensitize
tumors to radiation in preference to normal tissues. We have extended our studies to examine the mechanism responsible for this radiosensitization, using the EMT6
tumor model. Our results confirm that
nicotinamide (1000 mg/kg) significantly enhances the radiation damage in this
tumor when given as a single
intraperitoneal injection 90 min before irradiation. The data also show that
nicotinamide does not directly sensitize hypoxic cells to radiation either in vitro or in vivo. Excising
tumors immediately after irradiation and exposing them to
nicotinamide (7 mM) for 24 h similarly failed to increase the radiation damage, implying that
nicotinamide does not inhibit the repair of radiation-induced potentially lethal damage.
Nicotinamide did, however, produce a decrease in the binding of [14C]-
misonidazole in
tumors, consistent with a reduction in the degree of tumor hypoxia. There was also an increase in mean
tumor cell fluorescence of
Hoechst 33342 in
nicotinamide-treated mice compared to that of controls, suggesting that the increase in
tumor oxygenation was probably a consequence of an increase in
tumor blood perfusion.