Quantitative Analysis of the Effects of Iododeoxyuridine and Ionizing Radiation Treatment on the Cell Cycle Dynamics of DNA Mismatch Repair Deficient Human Colorectal Cancer Cells

摘要

DNA mismatch repair (MMR) is involved in processing DNA damage following treatment with ionizing radiation (IR) and various classes of chemotherapy drugs including iododeoxyuridine (IUdR), a known radiosensitizer. In this study, we have developed asynchronous probabilistic cell cycle models to assess the isolated effects of IUdR and IR and the combined effects of IUdR+IR treatments on MMR damage processing. We used both synchronous and asynchronous MMR-proficient/MMR-deficient cell populations and followed treated cells for up to 2 cell cycle times. We have observed and quantified differential cell cycle responses to MMR damage processing following IR and IUdR+IR treatments, principally in the duration of both G1 and G2/M cell cycle phases. The models presented in this work form the foundation for the development of an approach to maximize the therapeutic index for IR and IUdR+IR treatments in MMR-deficient (damage tolerant) cancers.