EFFECT OF ACTIVATED OXYGEN SPECIES IN HUMAN-LYMPHOCYTES

The cytogenetic effectiveness of activated oxygen species (AOS) genera ted by the superoxide forming xanthine-xanthine oxidase (X/XO) system was studied in human lymphocyte cultures. The observed chromosome dama ge was exclusively of the chromatid type. In the experiments a clear d ependence of aberration induction on XO concentration and exposure tim e could be demonstrated. While using anti-AOS agents, the H2O2 antagon ist catalase and the hydroxyl radical scavenger formate reduced X/XO i nduced chromosome damage whereas superoxide dismutase (SOD) did not. I n the presence of SOD, aberration frequency was even enhanced. The res ults indicate that the chromosome damage is caused indirectly via H2O2 formation from spontaneous dismutation of superoxide, whereas H2O2 mi ght be reduced intracellularly giving rise to the highly reactive hydr oxyl radical. This effect might be enhanced by SOD, possibly by raisin g the intracellular amount of easily membrane passing H2O2. Thus, refe rring to chromosome aberrations, SOD, which is generally reported to p rotect from AOS, is capable of increasing oxygen mediated biological d amage. This observation might be explained by the involvement of DNA a ssociated transition metal, like iron or copper ions, in reducing H2O2 . DNA bound copper ions, thought to be necessary for maintenance of DN A quaternary structure, might represent a generator complex for the hy droxyl radical by reduction of X/XO derived hydrogen peroxide. This mi ght cause 'site specific damage' to the DNA which is subsequently conv erted into chromatid-type aberration by S-dependent misreplication and /or misrepair. This is different to the formation of radiation induced chromosome aberrations which arise by an S-phase independent mechanis m.