DNA repair and cancer. In: Oxidative stress in aging.

Cancer cells have undergone several distinct transformational events leading to alterations of the normal growth and proliferation regulatory pathways. The probabilities of these events are increased by agents that damage and mutate DNA. It is now well established that oxygen is one such mutagen. Within the cell, the metabolic conversion of oxygen to reactive forms, particularly the hydroxyl radical, is an initial step in this process. Hydroxyl radical-mediated oxidative damage to DNA results in a variety of mutagenic lesions. However, this is a normal occurrence in every cell, and a host of proteins is involved in surveillance of the genome and removal of the damage. The link between DNA oxidative damage and cancer is evident from animal models lacking these DNA repair and antioxidant proteins. Mice deficient in repair of DNA oxidative damage or reactive oxygen species (ROS) detoxification typically are susceptible to cancer. Mitochondria, as a major source of intracellular ROS, and organelles essential for the maintenance of metabolic homeostasis, can also play critical roles in the initiation and promotion of cancer. Important mechanistic details of mitochondrial participation in tumori-genesis have recently been uncovered.