The Distance over Which a Misonidazole Molecule Can Trap Mobile Electrons in DNA

Abstract

In a recent paper Al-Kazwini et al. (1) identified two emissions of approximately equal intensity from DNA during irradiation. One of these emissions was unaffected by the presence of misonidazole in the DNA while the other component was quenched by increasing concentrations of the molecule. It was suggested that the quenching occurred when energy/charge released by the radiation damage to the DNA was trapped by the misonidazole molecule and that the range over which trapping could occur was about 25 base pairs. From the concentrations of misonidazole in the DNA it is possible to calculate the distance from a site of radiation damage in the DNA to the nearest misonidazole molecule, assuming that these molecules are placed at random. It is to be assumed here that the misonidazole molecule acts as a potential well such that, if at least one misonidazole molecule lies within n base pairs of the damaged site, the molecule acts as sink resulting in the quenching of one of the emissions. The method of calculation is as follows: Assume that each interaction of the radiation with the DNA is isolated, that is, the hits are very widely separated, and choose a long segment of DNA in which this hit occurs. In this study a length of 5000 base pairs was used. The hit was positioned at the center of this segment. Since the damage to the DNA by the ionizing radiation can extend for several base pairs (2), the hit region was taken to be 5 base pairs in length. Next, given the number of misonidazole molecules per base pair, the total number of these molecules in the chosen segment can be calculated. Each of these can be placed within the selected 5000 base pair fragment by drawing random numbers between I and 5000. It is now straightforward to check these positions relative to the position of the hit and ask if the hit lies within n base pairs of a misonidazole molecule. The calculation was terminated when the first molecule lying within the selected distance was found. The calculation was repeated for 1000 DNA fragments, putting the misonidazole molecules at new positions each time. The fraction of fragments in which the radiation hit lay within n base pairs of at least one misonidazole was determined.