Tissue damage by oxygen radicals

Radicals may interact with any compounds present in the cell, and the result may be initiation of cancer, heritable mutations, atherosclerosis and coronary heart disease or autoimmune disease. The most important, and potentially damaging, such interactions are:

1 With DNA in the nucleus, causing chemical changes in the nucleic acid bases (section 9.2.1) or breaks in the DNA strand. This damage may result in heritable mutations if the damage is to ovaries or testes, or the induction of cancer in other tissues. Although much damage to DNA is detected and repaired by the DNA repair system in cells, some will escape detection.

2 With individual amino acids in proteins. This results in a chemical modification of the protein, which may therefore be recognized as foreign by the immune system, leading to the production of antibodies against the modified protein that will also react with the normal, unmodified body protein. This may be an important factor in the development of autoimmune disease.

3 Some modified amino acids (e.g. dihydroxyphenylalanine) are capable of undergoing non-enzymic redox cycling, resulting in the production of more oxygen radicals.

4 With unsaturated fatty acids in cell membranes. This leads to the formation of dialdehydes, which react with DNA, causing chemical modification, and hence may result in either heritable mutations or initiation of cancer. Dialdehydes can also react with amino acids in proteins, leading to modified proteins that stimulate the production of autoantibodies.

5 With unsaturated fatty acids or amino acids in LDL (section 5.6.2.2). Oxidized LDL are not recognized and taken up by the LDL receptors in the liver but are recognized and taken up by scavenger receptors in macrophages. Macrophage uptake of LDL is unregulated, and the cells become engorged with lipid. These lipid-rich macrophages (called foam cells, because of their microscopic appearance) then infiltrate the epithelium of blood vessel walls, leading to the development of fatty streaks, and eventually atherosclerosis.

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