Telomere staining of human chromosomes and the mechanism of radiation-induced dicentric formation.

ABSTRACT

The majority of models of radiation action developed over the past half century hold that the curvilinear dose responses exhibited by eukaryotic cells to sparsely ionizing radiations result from the interaction of pairs of lesions produced in sensitive targets of the cell. Within this conceptual framework, chromosomal exchange aberrations (e.g., interchanges) are believed to occur through the interaction of damaged sites on both chromosomes participating in the exchange. In contrast, the model proposed by Chadwick and Leenhouts (as well as some other models) suggests that such exchanges arise from initial radiation damage to only one chromosome, which then becomes associated with an undamaged chromosome. A particular aspect of this theory is that asymmetrical exchanges, such as dicentrics, may be formed from the rejoining of a broken end of one chromosome to the telomere of another. By using a DNA probe that specifically hybridizes to the telomeric region of human chromosomes, we were able to test this assertion directly. After scanning more than 200 dicentrics produced in normal human fibroblasts by 6 Gy of 60Co gamma rays, virtually none were found that contained telomeres located between the centromeres of this aberration type. Therefore, since the proposed telomere-break rejoining process, per se, is not necessarily a central element of the Chadwick-Leenhouts model, we suggest the theory be modified to exclude this mechanism.