Internal hazards: baseline DNA damage by endogenous products of normal metabolism.
Recent improvements in the ability to detect chemically modified bases in DNA have revealed that not only does the genetic material incur damage by foreign chemicals, but that it also sustains injury by reactive products of normal physiological processes. This review summarises current understanding of the DNA-damaging potential of various substances of endogenous origin, including oxidants, lipid peroxidation products, alkylating agents, estrogens, chlorinating agents, reactive nitrogen species, and certain intermediates of various metabolic pathways. The strengths and weaknesses of the existing database for DNA damage by each class of substance are discussed, as are future strategies for resolving the difficult question of whether endogenous chemicals are significant contributors to spontaneous mutagenesis and cancer development in vivo.
Department of Clinical and Experimental Pharmacology, The University of Adelaide, Adelaide, SA 5005, Australia. pburcham@medicine.adelaide.edu.au
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D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism; D000477:Alkylating Agents / Q000737:chemistry / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D002713:Chlorine / Q000378:metabolism; D004249:DNA Damage; D004967:Estrogens / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism; D009584:Nitrogen / Q000378:metabolism
D000447:Aldehydes; D000477:Alkylating Agents; D000596:Amino Acids; D004967:Estrogens; D005609:Free Radicals; D008054:Lipid Peroxides; D006418:Heme; D002713:Chlorine; D009584:Nitrogen