Sensitivity of exponentially growing populations of Escherichia coli to photo-induced psoralen-DNA interstrand crosslinks

Experimental survival curves for Escherichia coli K 12 (CR 34) were determined after exposure to 4,5',8-trimethylpsoralen and near ultraviolet light. The lethal action was shown to arise exclusively from interstrand crosslinks, cell vulnerability increasing markedly with the doubling time of the culture. To account for these results, two quite different models are considered. The first assumes that a cell survives as long as at least one copy of its genome remains undamaged; a variant of this permits repair by DNA strand exchange. The second model allows for a limited period of time during which DNA repair can take place. A crosslink in a stretch of DNA due to be replicated within this interval constitutes a fatal lesion. Theoretical survival curves are computed for bacterial populations with defined age distributions and chromosome configurations. While the first model completely fails to provide a satisfactory description of the experimental results, the second model does predict the presence of a shoulder in the survival curves and, in one of its forms, it seems to agree rather well with the measured data over a wide range of crosslink concentrations and doubling times.