Role of Different Enzymes in HO 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 (HO), which can function as a signaling molecule in extra- and intracellular signaling. To enhance our understanding of how various enzymes regulate cellular HO levels, we created a mathematical model of HO 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 HO variously, which results in differences in HO 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 HO. Analysis of results from model simulations for colorectal, lung, and breast cancer cell lines indicated that radiosensitive cell lines exhibited elevated levels of HO, attributed to the reduced efficiency of neutralizing enzymes. By highlighting cell-type-specific differences in HO neutralization, our findings may contribute to a deeper understanding of redox regulation in cancer cells and reveal new potential correlations with radioresistance.