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DNA Repair

The dark side of oxigen

How free radicals cause DNA damage ?

 

When exposed to ionizing radiation, the genetic DNA molecule may incur several damages. A single or double strand in the double helix molecule may break, or a base loss may occur (Fig. 12, 22b). Each day each cell suffers about 10,000 DNA injuries resulting from exposure to free radicals produced by routine metabolic activity within the cell, exogenous toxic chemical agents, or ionizing radiation.

Fortunately, the cell has a highly efficient DNA-repair mechanism for single-strand breakage. While the other strand holds the chromosomes together, the body immediately begins to repair the breakage. This is usually accomplished within about 2 to 8 hours. However, if more complex DNA damage occurs, the genetic problem may become very serious.

Radiation induced chromosomal abnormality does not always kill the cell in which it persists, nor does it always prevent mitotic division in the cell. However, when the injured cell reproduces, the same genetic injury persists in the new cells. Studies of atom-bomb survivors have shown that these chromosomal abnormalities may persist 40 years after the initial exposure. Residual unrepaired and mis-reparied chromosome damage in human blood samples has been experimentally demonstrated in acute radiation doses as low as 2 rads (Lloyd et al., 1988). Extensive studies have shown that no dose or dose rate of ionizing radiation is safe (Gofman, 1990; UNSCEAR< 1993).

DNA repair mechanisms is a subject that has become of major importance in cancer research in recent years. The p53 gene was elected in 1994 as the "Molecule of the Year" by Science, (Culotta and Koshland, 1994; Koshland, 1994) because of its important role in the repair mechanism of the DNA molecule and in the suppression of tumor growth. Normal DNA is critical to the maintenance of our health, and the very survival of the human species, yet it is vulnerable to environmental hazards. The DNA genome is believed to provide the blueprint for about 60,000 proteins that help keep us alive and healthy. If the DNA molecule were not properly replicated to the extent it is, the incidence of cancer would be much higher. The DNA molecule in every cell of the body is being damaged every second. Every cell loses more than 10,000 bases per day from the spontaneous breakdown of the DNA molecule. As each cell undergoes division and thereby copying DNA, each such event introduces the chance of error. Every exposure to a carcinogen enhances the further chance of injury to the DNA molecule and the possibility of further mutational changes. When one considers the overall potential for mutational damage throughout the body, the DNA damage resulting in mutational changes is truly staggering.

If DNA damage were permitted to go unchecked, the cells would cease to operate properly, and malignancies would soar out of control. Ultimately, an estimated 80-90 percent of the cancers are due to DNA damage (Sancer, 1994). Fortunately, the DNA repair enzymes in the body, under normal circumstances, are able to repair most, but not all, of the damage. Throughout the process of cell division, the DNA is constantly being scanned by the repair enzymes for mistakes. When damaged pieces of DNA are found, they are sliced out and repaired.

Multiple repair enzymes and metabolic pathways are now known to exist, and each specializes in a specific type of damage control. If mismatching of the DNA bases occur during the copying process, repair genes specialize in repairing mismatched errors. If that mismatching repair system fails to properly scan and delete the defective DNA pieces and repair the defect, cancer may result. A major goal of research today is to develop diagnostic tests that will detect defective mismatch repair genes. Normal metabolic activities produce free radicals and injure DNA through oxidation and other chemical reactions. Normal cells undergo a process known as apoptosis, or programmed cell death, but cancerous cells apparently are not subject to apoptosis which partially explains why malignant cells run out of control (Cullota and Koshland, 194).

A great deal of information is now available about DNA repair nutrients, antioxidants and free radical scavengers.


Source:Free Radicals Test