Genotoxic effects of high-energy iron particles in human lymphoblasts differing in radiation sensitivity

The effects of Fe-56 particles and Cs-137 gamma radiation were compared in TK6 and WTK1 human lymphoblasts, two related cell lines which differ in TP5 3 status and in the ability to rejoin DNA double-strand breaks. Both cell l ines were more sensitive to the cytotoxic and clastogenic effects of Fe-56 particles than to those of gamma rays. However, the mutagenicity of Fe-56 p articles and gamma rays at the TK locus was the same per unit dose an was h igher for gamma rays than for Fe-56 particles at isotoxic doses. The respec tive RBEs for TK6 and WTK1 cells were 1.5 and 1.9 for cytotoxicity and 2.5 and 1.9 for clastogenicity, but only 1 for mutagenicity. The results indica te that complex lesions induced by Fe-56 particles are repaired less effici ently than gamma -ray-induced lesions, leading to fewer colony-forming cell s, a slightly higher proportion of aberrant cells at the first division, an d a lower frequency of viable mutants at isotoxic doses. WTK1 cells (mutant TP53) were more resistant to the cytotoxic effects of both gamma rays and Fe-56 particles, but showed greater cytogenetic and mutagenic damage than T K6 cells (TP53(+)). A deficiency in the number of damaged TK6 cells (a) rea ching the first mitosis after exposure and (b) forming viable mutants can e xplain these results. (C) 2001 by Radiation Research Society.