Calculation of hydroxyl radical attack on different forms of DNA.

A stochastic model of hydroxyl radical reaction with the DNA macromolecule in dilute aqueous solution is presented. It is based on the Monte Carlo method, the model of Smoluchowski, the model of the regular DNA atomic structure and the knowledge of reaction rate constants for .OH radical reaction with DNA constituents. The calculated respective overall probability of .OH radical reaction with sugar or base moiety dependents on DNA form (A, B or Z), base composition (AT/GC content) and strandedness (single and double). While for all three DNA forms studied (A, B and Z) as well as for both single- and double-stranded B-DNA, the specific probability of .OH radical attack on nucleobases is modulated by their sequence, the attack on deoxyriboses is only slightly sequence dependent (except for Z-DNA). The model predictions are compared to the experimental patterns of strand breaks and alkali revealed breaks for single and double stranded DNA in B-form and discussed in terms of molecular mechanisms of DNA damage induced by hydroxyl radical.