DNA SINGLE-STRAND BREAKS BY AROMATIC NITROSO-COMPOUNDS IN THE PRESENCE OF THIOLS

Aromatic nitroso compounds, nitrosobenzene (NB), N,N-dimethyl-4-nitros oaniline (DMNA) and 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS), ca used DNA single strand breaks in the presence of thiol compounds. The strand breaking was inhibited completely by free radical scavenger eth anol. Electron spin resonance (ESR) studies showed that hydronitroxyl (or sulfur-substituted nitroxyl) radicals were generated in the early stage of the interactions. Formation of these radicals was not inhibit ed by ethanol, indicating that these radicals did not directly contrib ute to the strand breaking, The DNA strand breaking was inhibited part ially by superoxide dismutase and catalase under the limited condition s, but not by removal of oxygen from or addition of metal chelators to the reaction mixture. By ESR-spin trapping technique using 5,5-dimeth yl-1-pyrroline-N-oxide (DMPO), the DMPO-OH spin adduct was detected. F ormation of the spin adduct was inhibited by superoxide dismutase and catalase. The hydronitroxyl (or the sulfur-substituted nitroxyl) radic als may reduce oxygen into active oxygen species and also transformed by themselves into other unidentified free radical species to cause th e DNA strand breaks.