Underprediction of visibly complex chromosome aberrations by a recombinational-repair ('one-hit') model

Purpose: Published low-LET FISH data were used to test two models of chromo some aberration production based on breakage-and-reunion or recombinational repair. Materials and methods: Randomness of DnTA double strand break induction and misrejoining is analyzed comprehensively and adopted as a working hypothes is. Proximity effects are approximated by using interaction sites. Model re sults are calculated using CAS (chromosome aberration simulator) Monte Carl o computer software with two adjustable parameters. CAS can emulate the spe cifics of any experimental painting protocol, allowing very detailed tests of the models. Results: To reasonable approximation, breakage-and-reunion model prediction s are consistent with low-LET FISH results. including two large, elaborate, one-paint data sets. An explicitly specified version of the recombinationa l-repair model severely underpredicts the frequency of the visibly complex aberration patterns most commonly observed with one-paint FISH, and is inco nsistent with some observed multi-paint patterns. When high-dose effects (d istortion and saturation) are taken into account quantitatively a dose-resp onse relation for apparently simple interchanges slightly favours the break age-and-re union model over the recombinational-repair model, despite being approximately linear over the dose range 2-6 Gy. Conclusion: The random breakage-and-reunion model gives comprehensive basel ine predictions that are sufficiently accurate for the organization of expe rimental results. The data speak against complex aberrations being formed b y the random recombinational repair pathway discussed here.