DNA synthesis inhibition of nitroxide radicals on leukemia cells

4-isothiocyanate-2,2,6,6-tetramethyl-piperidine-1-oxyl has the strongest effects on the DNA synthesis and viability of isolated leukemia 7712 cells. This compound is a very potent inhibitor of DNA synthesis with 50% inhibition of cell DNA synthesis occurring at 2.2 micrograms/ml, while the LD50 for white mice is 277 mg/kg. During the concentration of 50 micrograms/ml, the inhibition of DNA synthesis is 99.7%, which is unable to damage the DNA replicate template. The inhibition of this compound, a combination of nitroxide and isothiocyanate, appears to be stronger than that of the sum of the two separate actions. Much more moderate effects are seen for all the other nitroxide radicals. After reducing nitroxide to hydroxylamine, there is no inhibition for DNA synthesis. The free radical mechanism of carcinogenesis and antitumor action has been discussed.