Sublethal damage, potentially lethal damage, and chromosomal aberrations in mammalian cells exposed to ionizing radiations

Abstract

Sublethal and potentially lethal damage are abstract terms that originated and were defined without reference to molecular and subcellular entities in which such radiation damage was registered. The establishment of a cause-and-effect relationship between chromosome fragment loss and cell killing by ionizing radiations, along with a substantial body of knowledge in radiation cytogenetics, allows a definition of these terms in a context where hypotheses become testable and progress toward a better understanding of these phenomena is more likely. Accordingly, the simplest hypothesis which best fits the observations is as follows. Most aberrations are exchange types requiring an interaction to form the exchange between two broken regions of a chromosome or chromosomes, that is, a break-pair. Very few single breaks fail to rejoin or restitute, so the vast majority are sublethal. Any such sublethal break may become a potentially lethal break-pair if another sublethal break occurs within some range where it is possible for the two to interact. The proportion of break-pairs in which a mis-repair event results in a lethal acentric fragment-producing exchange, can be altered depending on treatment conditions. Such conditions change the balance between “PLD repair” and “PLD fixation.” Studies on the control of radiosensitivity have focused on differences in repair processes, but large differences in radiation response may just as well occur with identical repair processes in operation but with different conditions of fixation.