title: Chronic inflammation and mutagenesis.
abstract: Inflammation is a necessary part of the immune response. However, when inflammation persists, the resultant state of chronic inflammation may have a number of secondary consequences associated with increased risk of chronic disease. Among these is an increased rate of mutation. There is evidence to suggest that the accumulation of reactive oxygen and nitrogen species may be a causal factor in chronic inflammation. These reactive species are also produced through the oxidative burst associated with the inflammatory process, and may interact with various cellular components including proteins, lipids and, most important for mutagenesis, nucleic acids. DNA strand breaks are commonly produced, leading to chromosomal mutation. Oxidized bases, abasic sites, DNA-DNA intrastrand adducts, and DNA-protein cross-links also occur. Not only do the nucleic acid products act directly as pro-mutagenic lesions, lipid peroxidation products may also lead to secondary DNA damage, including pro-mutagenic exocyclic DNA adducts. While frameshift and chromosomal mutations have been associated with chronic inflammation, much of the evidence reveals base pair substitution mutations associated with polymerase stalling near the lesions, and base pair mis-incorporation. There are also indirect effects of ROS/RNS through inhibition of DNA repair enzymes and/or effects on metabolic activation of known carcinogens. Certain disease states, including the Inflammatory bowel diseases, Crohn's disease and ulcerative colitis are associated with enhanced levels of chronic inflammation, and show evidence of enhanced levels of genetic damage in the colonic mucosa. Mutations may provide at least part of the cause of enhanced susceptibility to chronic diseases associated with chronic inflammation.
authors.affiliation: Discipline of Nutrition and ACSRC, FM&HS, The University of Auckland, Auckland, New Zealand. lferguson@auckland.ac.nz
authors.forename: Lynnette R
authors.initials: LR
authors.lastname: Ferguson
mesh_terms: D002908:Chronic Disease; D004249:DNA Damage; D004198:Disease Susceptibility; D044127:Epigenesis, Genetic; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000235:genetics; D023421:Models, Animal; D016296:Mutagenesis; D018384:Oxidative Stress / Q000235:genetics; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species