Studies of the toxicity and radiosensitising activity of triacetoneamine-N-oxyl in mice

Leukaemic CBA mice were injected intravenously with 6·8 mg of triacetoneamine-N-oxyl (TAN) three minutes before killing and exposure to single doses of X rays in the range 1,000–3,000 R. Immediately after exposure, leukaemia cells were extracted from the infiltrated livers of the mice and assayed for determination of the fraction of cells surviving. In controlled studies there was no evidence that pretreatment of the mice with TAN had increased the sensitivity of the leukaemia cells. Mice receiving repeated intraperitoneal sublethal doses of TAN displayed considerably increased tolerance of the drug when the interval between doses was 90 minutes or longer, indicating that the drug is excreted or destroyed at a moderately fast rate in vivo. The radiosensitising capacity of TAN for anoxic bacteria was not measurably reduced after incubation of the drug for one hour with a dense suspension of metabolising tumour cells. Erythrocytes were used to show that TAN passes through the cell membrane and that its sensitising action on anoxic bacteria is not degraded in the presence of a high concentration of haemoglobin.