Chromatid breaks in human cells represent the apparent interstitial loss of up to about 40 Mbp of DNA, difficult to account for as single lesions under the classical 'breakage-and-reunion' hypothesis. If breakage-first resulted from two interacting DNA double-strand breaks (dsb) with the loss or displacement of the intervening fragment, a dose-squared relationship would be predicted for chromatid breaks. However, the relationship between chromatid break frequency and dose for human cells is linear. The alternative 'exchange' model of Revell is based on the principle of the interaction of two initiating lesions, thus also predicting a dose-squared relationship for chromatid 'breaks'. The signal model explains the conversion of dsb into chromatid breaks on the assumption that a single dsb generates a signal which triggers the cell to initiate a recombinational exchange involving a large loop of chromatin. Incomplete exchanges would be observed as chromatid breaks. Possible candidates for the signalling molecule(s) are DNA protein kinase (DNA PK) and the ATM protein.

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Treatment of X-irradiated stationary Ehrlich ascites tumour cells with the DNA synthesis inhibitor beta-ara A (120 mumol/l, 30 min before and for 7 hours after irradiation) is shown to lead to a large increase in the incidence of anaphase chromosome abnormalities (anaphase bridges and fragments) at the first mitosis following irradiation. This increase is similar to the increase in cell killing observed for this cell line when treated with beta-ara A under the same conditions (Iliakis 1980). The results suggest that the increased frequency of chromosome abnormalities caused by beta-ara A may result not only from the inhibition of DNA double strand break repair, leading to additional unrepaired d.s.b. (Bryant and Blöcher 1982) and chromosome deletions, but also from an increase in the frequency of misrepair of d.s.b. leading to exchange aberrations.