Radiation-Like Modification of DNA and H2O2 Formation by Activated Human Polymorphonuclear Leukocytes (PMNs)
Active oxygen species generated by stimulated PMNs were found to be mutagenic and carcinogenic (1,2). We (3–5) and others (6,7) have shown that oxygen species produced by phagocytic cells are capable of modifying bases in DNA exposed to them. Those identified to date are 5-hydroxymethyl uracil (HMU) (3–5), thymine glycol (TG) (4–6) and 8-hydroxyguanine (BOHG) (7). All of them are known to be formed by the action of ionizing radiation (8–11). HMU and TG are excreted in the urine by humans and rats which points to these thymine derivatives as products of the normal biological processes (12), That these oxidized DNA base derivatives are potentially harmful to the well-being of humans and animals is shown by the existence of the repair enzymes HMU- and TG-glycosylases in mammalian cells (13–16). There is also evidence that 80HG might be repaired as well (11). However, when removal of abnormal bases from DNA is not complete or timely, they have the potential to exert their deleterious effects. For example, TG is thought to provide a replication block (17,18), whereas, HMU and particularly its deoxyribonucleoside HMdU are mutagenic (19). HMdU, which is known to be incorporated into cellular DNA, is also cytotoxic and cytostatic to a number of mammalian cells, and acts as a radiomimetic agent as it causes diarrhea and leukopenia, symptoms of acute radiation sickness (20–23). Thus PMNs, whose role is to protect against invading bacteria or other opsonized particles, are capable of imparting a radiation-like damage, certain types of which might be heritable.
KeywordsHeLa Cell Active Oxygen Species Human Polymorphonuclear Leukocyte Autologous Plasma Normal Biological Process
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