Changes in Chromosome Structure induced by Radiations: a Test of the Two Chief Hypotheses

Abstract

Two hypotheses have been advanced to suggest how radiation may produce chromosome aberrations. The classical “breakage-first” hypothesis due to Sax¹ and others (reviewed in ref. 2) is that the initial lesion is a break in the chromosome. The two ends produced may then (1) rejoin in the original configuration (restitution); (2) rejoin “illegitimately” with other ends produced by another break to form an exchange; or (3) remain unjoined to form a terminal deletion. Revell's exchange hypothesis³ is that all chromatid aberrations are exchanges produced by the interaction of two lesions (not breaks). The aberrations involving only one chromosome are produced only at the point of overlap where the chromosome is looped back on itself. The two proposals differ principally in that the exchange hypothesis proposes (1) that the initial lesion is not a break, (2) that all aberrations are exchanges involving two lesions, and (3) that all aberrations except exchanges between different chromosomes are formed at the point of overlap where the chromosome is in a loop. Chromatid deletions, which are unrejoined breaks on the breakage-first hypothesis, in Revell's hypothesis result from the failure to complete an exchange at the point of overlap of a loop in the way known to occur frequently when exchanges are produced between chromosomes. Attempts to distinguish between these two hypotheses have centred on the relative frequencies of the different kinds of aberrations and on the dose response relationships. Results have been equivocal: some of the data do not agree with the simple statements of either the breakage-first^4–7 or the exchange hypotheses^8–12. We report here a more direct test of the differences between the two hypotheses. We have not explored the nature of the initial lesion, but have shown that many terminal deletions are actually incomplete exchanges. The data agree both qualitatively and quantitatively with Revell's exchange hypothesis.