Hypoxia-mediated Selection of Cells with Diminished Apoptotic Potential

Cancer: Necrosis vs. Apoptosis Cancer is the second leading cause of death in humans. A cancer cell is a cell that has mutated from its original form and will often grow at a more rapid rate than normal. The body has built certain mechanisms to protect itself from these types of cells. One of the physiological processes the body uses to kill off these cells is apoptosis. Apoptosis is sometimes called "cell suicide". When the body detects that a cell's DNA has mutated and cannot be repaired, the cell will somehow trigger itself to self destruct. Up until 1972, scientists hadn't really looked carefully at how cells die. Once they did, it was apparent that two things could happen: necrosis or apoptosis. Necrosis was the term used to describe all cells that had died. However scientists have found that necrosis and apoptosis are two different processes. Necrosis is a result of outside forces acting upon a cell, causing it's destruction. Upon destruction of the cell in this manner, the internal contents of the cell are leaked into the local environment, which can be extremely harmful. In contrast, a cell dying by apoptosis does not release it's contents and potentially harm neighboring cells. Apoptosis is actually an active process within the cell. A process triggers some other process (which is not quite clear) inside the cell and tells the cell to start disassembling itself. When this happens, instead of releasing harmful chemicals into its environment, the cell is thought to send parts of itself to other surrounding cells to digest it. Roles of p53 and bcl-2 in Apoptosis The authors above and other scientists believe that the expression of the p53 gene is required for apoptosis. The p53 gene has been labeled as the tumour su... ... increases as oxygen is reduced, those cells with mutated p53 have a slower increase in death rate in hypoxic regions, compared to those cells that have normal p53 expression. This seems to point to the fact that the hypoxic regions are actually setting up a natural selection for the p53 deficient cells, and possibly other mutations resistant to death. Treatment Problems This can cause a problem when treating these cells with radiation and chemotherapy. These treatments attack the cells and attempt to destroy the DNA within the cell. This will usually cause an increase in the rate of apoptosis within the area treated. However if the cells in the area have built up a resistance to apoptosis they have built up an effective resistance to the chemotherapy and radiation. These facts could explain why the p53 gene is the most commonly mutated gene in human cancer.