Recovery of Human Lymphocytes Damaged with γ-Radiation or Enzymatically Produced Oxygen Radicals: Different Effects of Poly(ADP-ribosyl)polymerase Inhibitors

Summary

Quiescent human lymphocytes were damaged in two different ways, both producing toxic oxygen radicals: xanthine oxidase plus hypoxanthine (XOD/HYP), or γ-rays. Under conditions where DNA synthesis was reduced to 10–20% of control, inhibitors of poly(ADP-ribosyl)polymerase (ADPRP, an enzyme that becomes activated in the presence of DNA strand breaks) allowed lymphocytes to recover completely when the damage was caused by XOD/HYP, but they did not affect DNA synthesis of irradiated cells. However, a protective effect of ADPRP inhibitors was observed with irradiated lymphocytes receiving doses ⩾ 50 Gy. Unscheduled DNA synthesis was significantly increased when lymphocytes were damaged by high radiation doses in the presence of ADPRP inhibitors. We suggest that ionizing radiation does not stimulate poly(ADP-ribose) synthesis in lymphocytes at doses that impair lymphocyte DNA synthesis by 80–90%, while ADPRP may be involved in the repair of DNA lesions occurring at higher radiation doses.