Chromosome aberrations, micronuclei, and activity of superoxide dismutasesin human lymphocytes after irradiation in vitro

The goal of this study was to provide data on the dose-dependent production of dicentrics and micronuclei in human lymphocytes irradiated with 22.6 Me V protons and to estimate the possible contribution of intracellular supero xide dismutases (SOD) to the relative biological effectiveness (RBE) of pro tons. For the dose-response study, heparinized whole blood of a healthy vol unteer was irradiated with protons and Xrays employing radiation doses of 0 .5-4 Gy. Three biological endpoints were analyzed: chromosomal aberrations, micronuclei, and specific activity of cytosolic (CuZnSOD) and mitochondria l (MnSOD) superoxide dismutases in harvested human blood cells. Dicentric d ose-response curves fit a linear-quadratic form (alpha = 0.094 +/- 0.006, b eta = 0.032 +/- 0.001) induced with X-rays and (alpha = 0.119 +/- 0.057, be ta = 0.029 +/- 0.014) for 22.6 MeV protons. Protons were more effective tha n X-rays in producing exchanges, particularly at 0.5 and 1 Gy. In contrast to X-ray irradiated samples where a significant increase in the specific ac tivity of MnSOD was recorded (up to a radiation dose of 1 Gy), irradiation with protons markedly reduced its activity. As a consequence of the reduced activity of MnSOD, the chromosomal dose-response curve became quadratic. T he RBE for dicentrics varies with dose (from 2.2 to 1.01) and reduced activ ity of MnSOD is an important contributor to the RBE of protons. SODs, parti cularly MnSOD, play an important role in defending DNA from reactive oxygen species. A reduced activity of SOD, particularly MnSOD, is an important co ntributor to the RBE of protons.