DNA single strand breaks by aromatic nitroso compounds in the presence of thiols.
Aromatic nitroso compounds, nitrosobenzene (NB), N,N-dimethyl-4-nitrosoaniline (DMNA) and 3,5-dibromo-4-nitrosobenzene sulfonate (DBNBS), caused DNA single strand breaks in the presence of thiol compounds. The strand breaking was inhibited completely by free radical scavenger ethanol. 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 inhibited by ethanol, indicating that these radicals did not directly contribute to the strand breaking. The DNA strand breaking was inhibited partially by superoxide dismutase and catalase under the limited conditions, but not by removal of oxygen from or addition of metal chelators to the reaction mixture. By ESR-spin trapping technique using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), the DMPO-OH spin adduct was detected. Formation of the spin adduct was inhibited by superoxide dismutase and catalase. The hydronitroxyl (or the sulfur-substituted nitroxyl) radicals may reduce oxygen into active oxygen species and also transformed by themselves into other unidentified free radical species to cause the DNA strand breaks.
Hiramoto
K
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.
Ojima
N
N
Kikugawa
K
K
D000818:Animals; D004249:DNA Damage / Q000187:drug effects*; D004277:DNA, Single-Stranded / Q000187:drug effects*; D005609:Free Radicals; D009603:Nitroso Compounds / Q000494:pharmacology*; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds
D004277:DNA, Single-Stranded; D005609:Free Radicals; D009603:Nitroso Compounds; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds