The damaging action of hydrogen peroxide on DNA of human fibroblasts is mediated by a non-dialyzable compound.

Single-strand breaks were formed in DNA when nuclei from human fibroblasts were incubated with buffered salt solutions containing H2O2. This had not been observed when purified DNA had been exposed to H2O2. The nuclear factor which mediates the action of H2O2 on DNA was removed when nuclei were dialyzed against buffered salt solutions containing EDTA. If this complexing agent was not present during dialysis, the factor remained in the nuclear preparation. The formation of DNA single-strand breaks was considerably diminished when nuclei were incubated in solutions containing H2O2 plus hydroxyl radical scavengers. These facts favor a scheme according to which H2O2 reacts with a metal-macromolecule complex in the nucleus giving rise to a hydroxyl radical which is the DNA-damaging agent. Therefore, hydrogen peroxide seems to be a mimetic chemical of ionizing radiation.