放射生物学核心 .pptVIP

Caffeine Radiosensitized the NHEJ Proficient and Deficient Cells Radiat Res. 159: 426, 2003 * Checkpoint inhibition does not directly affect NHEJ but radiosensitizes cells. Does checkpoint activation facilitate HRR, therefore, radiosensitize cells? * Today we turn to another type of lesion of direct relevance not only to radiation oncology, but also to medical oncology. DNA dsb are considered the lesions that lead to cell death, transformation and mutation after exposure to ionizing radiation. Although many chemotherapeutic agents act by inducing other forms of damage, some very promising novel compounds act by ultimately inducing DNA dsb. Thus, the topic is of central importance for radiation oncology and of considerable importance in Medical Oncology. But before proceeding with the cellular responses to this type of damage, lets run through some fundamental definitions. * The sources of DNA dsb can be divided in endogenous and exogenous. The outline indicates that cell have to cope with DNA dsb very frequently. Cells have therefore developed ways to cope with the generation of dsb in their genome. * * * Ionizing Radiation-Induced Checkpoint and DNA RepairYa Wang, Ph.D.(12-2004)Thomas Jefferson UniversityPhiladelphia, USA * Cell Cycle Checkpoints: Definition Checkpoints are biochemical pathways. Checkpoints regulate the progression, in terms of order and timing, of cells from one phase of the cell cycle to the next (normal checkpoint). Checkpoints slow down the progression of cells through the cycle after DNA damage (DNA damage-induced checkpoint) * The DNA Damage Checkpoints in the Cell Cycle , DNA damage reagents * ATM and ATR are two of the most important checkpoint proteins in mammalian cells. * The ATR/CHK1 pathway pathway plays a major role in DNA damage-induced checkpoint regulation and cell survival: JBC 276: 17693, 2001 Cancer Res. 62: 1598, 2002 Cancer Res. 62: 2483, 2002 Cancer Res. 62: 6031, 2002 Oncogene 21: 6377,