Complex chromosomal rearrangements induced in vivo by heavy ions

Abstract

It has been suggested that the ratio complex/simple exchanges can be used as a biomarker of exposure to high-LET radiation. We tested this hypothesis in vivo, by considering data from several studies that measured complex exchanges in peripheral blood from humans exposed to mixed fields of low- and high-LET radiation. In particular, we studied data from astronauts involved in long-term missions in low-Earth-orbit, and uterus cancer patients treated with accelerated carbon ions. Data from two studies of chromosomal aberrations in astronauts used blood samples obtained before and after space flight, and a third study used blood samples from patients before and after radiotherapy course. Similar methods were used in each study, where lymphocytes were stimulated to grow in vitro, and collected after incubation in either colcemid or calyculin A. Slides were painted with whole-chromosome DNA fluorescent probes (FISH), and complex and simple chromosome exchanges in the painted genome were classified separately. Complex-type exchanges were observed at low frequencies in control subjects, and in our test subjects before the treatment. No statistically significant increase in the yield of complex-type exchanges was induced by the space flight. Radiation therapy induced a high fraction of complex exchanges, but no significant differences could be detected between patients treated with accelerated carbon ions or X-rays. Complex chromosomal rearrangements do not represent a practical biomarker of radiation quality in our test subjects.

Cytogenetic Biomarkers of Radiation Exposure

“…The biological reason for this long-term survival of such heavily damaged PBLs is unclear. However, similar observations, at varying frequencies, have been reported elsewhere including in plutonium workers [87][88][89][90], thorotrast patients [85,91], veterans of nuclear testing [92], A-bomb survivors [93], astronauts and patients receiving carbon therapy [81]. Interestingly, Hande et al [79] found a significant correlation with estimated plutonium dose to the bone marrow (from ~500mGy) and yield of complex aberrations suggesting quantification could potentially be used for dose reconstruction.…”

Expression of p53-Regulated Genes in Cultured Mammalian Cells After Exposure to A Space Environment

“…Slides were stained with either Giemsa for dicentric analysis, or painted with whole-chromosome DNA probes for fluorescent in-situ hybridization (FISH). The increase in aberrations during long-term missions was consistent with the values calculated from physical dosimetry data (Durante et al, 2004). In the present project, chromosomal analysis will be performed by examining chromosomal structure and also by utilizing immunohistochemistry.…”

The Biological Effects of Space Radiation during Long Stays in Space

“…Mutations induced by space radiation could lead to carcinogenesis. The types of chromosomal aberrations induced by space radiation were translocations and complex exchanges seen in the cytogenetic analysis of lymphocytes of astronauts (Durante et al, 2003(Durante et al, , 2004George et al, 2002). Large individual differences in the frequency of these types of chromosomal aberrations were observed among astronauts.…”