Kinetic Modeling Reveals the Roles of Reactive Oxygen Species Scavenging and DNA Repair Processes in Shaping the Dose-Response Curve of KBrO₃-Induced DNA Damage

Figure 2

Base model simulation results. (a) Model used for simulation of 8-OH-dG formation in absence of any DNA repair mechanisms. (b) Base Model used for simulations of DNA adducts and SSB formation in the presence of a BER repair mechanism. (c) Time course of KBrO₃ exposure, 8-OH-dG, and SSB levels determined by simulations using the model in (b). A brief period of KBrO₃ exposure (blue) in the presence of GSH, followed by quick KBrO₃ removal. A base excision repair (BER) mechanism is active (b). The time course of 8-OH-dG adducts (green) shows a fast initial increase of adducts and consequent decrease as the BER repairs the adducts. However, infrequent repair failure results in persistent single strand breaks (SSB) that gradually accumulate over the course of the simulation (red). (d) A dose-response plot sectioned from a time point marked in (c) (dashed line) shows that the SSB response can be linear despite the nonlinear, threshold-like appearance of the 8-OH-dG adducts.

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