Formation of 8-hydroxydeoxyguanosine, hydroxyl free radical adduct of DNA in granulocytes exposed to the tumor promoter, tetradecanoylphorbolacetate.

The exposure of human granulocytes to the tumor promoter, tetradecanoylphorbolacetate (TPA), resulted in the accumulation of 8-hydroxydeoxyguanosine (8-OHdG) in the DNA of the treated cells. Hydroxyl free radicals react with DNA causing the hydroxylation of guanine at the C-8 position. The modified nucleoside (8-OHdG) cleaved from DNA, was quantitated at subpicomole levels utilizing high pressure liquid chromatography with electrochemical detection (LCED). Superoxide dismutase and catalase caused a marked decrease in the levels of 8-OHdG in the cellular DNA. The level of 8-OHdG formed by TPA stimulation of granulocytes was equivalent to one modified guanine for about every 600 possible guanines in the cellular DNA.