Role of Different Enzymes in H2O2 Neutralization and Cellular Radioresistance, Estimated by Mathematical Modeling

Reactive oxygen species (ROS) are fundamental components found in cells that exist in an oxygen environment. While they are often viewed as detrimental metabolic byproducts that can harm cells, leading to aging and cell death, they can also play a role in cellular regulatory processes and have beneficial effects. One of the main ROS present in all cells is hydrogen peroxide (H₂O₂), which can function as a signaling molecule in extra- and intracellular signaling. To enhance our understanding of how various enzymes regulate cellular H₂O₂ levels, we created a mathematical model of H₂O₂ neutralization and performed computer simulations to estimate the neutralization efficiency in various types of cells. Data on gene expression for genes participating in this process were incorporated into the calculations, along with the regulation of enzymes in oxidation and reduction processes. The conducted simulations demonstrate that cells originating from different tissues utilize systems neutralizing H₂O₂ variously, which results in differences in H₂O₂ cellular levels. The simulation findings suggest that the differences in radiosensitivity seen in various cancer cell types may be linked to their effectiveness in scavenging H₂O₂. Analysis of results from model simulations for colorectal, lung, and breast cancer cell lines indicated that radiosensitive cell lines exhibited elevated levels of H₂O₂, attributed to the reduced efficiency of neutralizing enzymes. By highlighting cell-type-specific differences in H₂O₂ neutralization, our findings may contribute to a deeper understanding of redox regulation in cancer cells and reveal new potential correlations with radioresistance.