Rejoining of isochromatid breaks induced by heavy ions in G(2)-phase normal human fibroblasts

We reported previously that exposure of normal human fibroblasts in G(2) ph ase of the cell cycle to high-LET radiation produces a much higher frequenc y of isochromatid breaks than exposure to gamma rays. We concluded that an increase in the production of isochromatid breaks is a signature of initial high-LET radiation-induced G(2)-phase damage. In this paper, we report the repair kinetics of isochromatid breaks induced by high-LET radiation in no rmal G(2)-phase human fibroblasts. Exponentially growing human fibroblasts (AG1522) were irradiated with gamma rays or energetic carbon (290 MeV/nucle on), silicon (490 MeV/nucleon), or iron (200 MeV/nueleon) ions. Prematurely condensed chromosomes were induced by calyculin A after different postirra diation incubation times ranging from 0 to 600 min. Chromosomes were staine d with Giemsa, and aberrations were scored in cells at G(2) phase. G(2)-pha se fragments, the result of the induction of isochromatid breaks, decreased quickly with incubation time. The curve for the kinetics of the rejoining of chromatid-type breaks showed a slight upward curvature with time after e xposure to 440 keV/mum iron particles, probably due to isochromatid-isochro matid break rejoining. The formation of chromatid exchanges after exposure to high-LET radiation therefore appears to be underestimated, because isoch romatid-isochromatid exchanges cannot be detected. Increased induction of i sochromatid breaks and rejoining of isochromatid breaks affect the overall kinetics of chromatid-type break rejoining after exposure to high-LET radia tion. (C) 2001 by Radiation Research Society.