Identification of hydroxyl radical-induced lesions in DNA base structure: biomarkers with a putative link to cancer development.
Hydroxyl radical-induced DNA base lesions of guanine and adenine were originally found in neoplastic and microscopically normal livers of fish exposed to environmental carcinogens. They were later identified in a mammalian tissue--the cancerous female breast. This evidence suggested that the base lesions are broadly present in the cancerous and microscopically normal tissues of a variety of eukaryotic organisms. The base lesion concentrations in both neoplastic tissues frequently exceeded 1 modified base in 1000 normal bases. By contrast, the base lesion:normal base ratios in healthy tissues were generally 10-100 times less. A greater variety of base lesions was found subsequently in the cancerous lung, brain, and other human tissues, although information relating to their biological significance is largely confined to the originally found purine derivatives. The biochemistry of the base lesions and the relationship of ring-opening (Fapy) derivatives to OH adducts in the DNA of normal and cancerous tissues is discussed with regard to the etiology of cancer and the potential use of the lesions as biomarkers for cancer risk assessment.
Malins
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Molecular Epidemiology Program, Pacific Northwest Research Foundation, Seattle, WA 98122.
D000225:Adenine / Q000378:metabolism*; D000818:Animals; D001482:Base Composition / Q000187:drug effects; D015415:Biomarkers; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D008401:Gas Chromatography-Mass Spectrometry; D006147:Guanine / Q000378:metabolism*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D017720:Molecular Epidemiology; D009369:Neoplasms / Q000209:etiology* / Q000378:metabolism; D012307:Risk Factors
D015415:Biomarkers; D004273:DNA, Neoplasm; D017665:Hydroxyl Radical; D006147:Guanine; D000225:Adenine