Is repair of DNA strand break damage from ionizing radiation second-order rather than first-order? A simpler explanation of apparently multiexponential repair.

摘要

The purpose of this paper is to suggest the hypothesis that repair of radiation damage might be largely a second-order process (binary), as well as or instead of first-order (monoexponential). Second-order means that the rate of repair is proportional to n(2) instead of to n, where n is the number of repairable breaks. Integrating this equation gives a linear plot of the reciprocal proportion of unrepaired lesions, n(0)(t), as a function of repair time. This is in contrast to mono- or biexponential processes which give rise to reciprocal plots not consistent with such linearity, except with specially selected distributions with multiple T((1/2))'s. There is the advantage of only one parameter (the first half-time) instead of (2n - 1) parameters for n components. At times greater than 2tau of the longest exponential component, a larger proportion of damage would be incompletely repaired than in a mono- or biexponential model of repair. Data on DNA repair from published laboratory experiments were reanalyzed. Results are presented as graphs of the reciprocal of the proportion of damage remaining as a function of time after irradiation of DNA. If the second-order process is correct, these graphs should be straight lines, even though traditional semilog plots of the same data are markedly concave upward, showing the well-noted slowing down of repair with time after irradiation. All the data sets found in the literature showed a good fit to a straight line representing reciprocal repair. Repair of single-strand breaks in DNA fitted very well, from 1.0 down to 1/40 of the initial damage remaining, with tau values of 5-10 min. Repair of DSBs fitted almost as well. One set of data showed a strong dependence on temperature in the range 10-37 degrees C, with each curve fitting the straight reciprocal plot. The tau values for DSBs were 10-100 min, of similar magnitude to those for repair of animal tissues. The second-order process with a single time parameter could explain the data showing "apparently slowing down" repair previously analyzed by multiexponential formulae requiring more parameters. It appears that second-order repair may play a larger part in repair processes than has usually been assumed. It is suggested that analysis of data on repair of radiation-induced damage could test the second-order (one-parameter reciprocal) analysis, as well as using bi-or multiexponential analyses. If repair in DNA is relevant to recovery in mammalian tissues, there may be serious clinical implications, to be discussed elsewhere.