The role of stable chromosome aberrations as biological indicators of radiation effect: studies in patients after total body irradiation and bone marrow transplantation.

Abstract

The so-called unstable aberrations measured primarily as dicentrics and ring chromosomes are very useful as indicators of human radiation exposure. The role of stable chromosomal aberrations as indicators of radiation effects is not yet known. Stable chromosome aberrations persist longer in radiation-exposed individuals because cells with monocentric aberrations (= stable) have a higher probability of survival after cell division than multicentric or acentric aberrations (= unstable). Aberrations were investigated in 89 patients with chronic myelogenous leukemia undergoing total body irradiation (TBI) for bone marrow transplantation (BMT). Serial follow-up investigations were performed in 31 patients by analyzing lymphocytes of the peripheral blood. Patients had TBI of 10 to 12 Gy as conditioning therapy for BMT. Stable anomalies were investigated by Giemsa-banding and karyotyping in addition to standard analysis. A very high number of cells with stable aberrations was found up to five years after TBI. Investigations of the blood showed that a considerable number of cells with stable aberrations derive from radiation-damaged and clonally expanded hemopoietic precursor cells. We conclude that stable aberrations are useful as indicators of radiation effects in human beings. Clonal stable aberrations represent cellular radiation effects conserved at the stem cell level. Stable aberrations should be analyzed not only by the use of fluorescence in situ hybridization with chromosome painting probes, but also by karyotyping. The latter is necessary to detect stem cell effects by proving the clonal expansion of chromosomal aberrations, and should be performed with the assistance of an automatic chromosome analysis system.