[DNA damage by oxygen radicals and carcinogenesis].
Oxygen radicals are produced by ionizing radiation and many other environmental carcinogens. They are also produced in cells endogenously by the oxygen metabolism. Therefore it appears to be important to study DNA damage by oxygen radicals and its relation with mutagenesis and carcinogenesis. During a study on DNA damage caused in vitro by heated carbohydrates, which were being used as a model of cooked foods, a new type of DNA modification was discovered, the formation 8-hydroxyguanine (8-OH-Gua). Various oxygen radical forming carcinogenic agents (radiation, cigarette smoke components, asbestos + H2O2 etc.) have been found to be effective in the formation of 8-OH-Gua in DNA in vitro. The formation of 8-OH-Gua was also observed in cellular DNA in vivo after mice or cultured cells were irradiated by ionizing radiation. The 8-OH-Gua residue in DNA may cause mutagenesis and carcinogenesis, since 8-OH-Gua in DNA induces misreading during DNA synthesis in vitro. Among the various types of DNA damage induced by oxygen radicals, 8-OH-Gua can be most readily measured at high sensitivity by high-pressure liquid chromatography coupled to an electrochemical detector. Recently, we found that oral administration of several chemical carcinogens, which are known to produce oxygen radicals, induce 8-OH-Gua in rat target organ DNA. Therefore, 8-OH-Gua can be used as a marker for monitoring oxidative DNA damage as a means of evaluating the carcinogenic potency of various oxygen radical forming agents. We are also measuring 8-OH-Gua levels in human lymphocyte DNA in order to investigate the relation between oxidative DNA damage and the incidence of cancer.
Kasai
H
H
Biology Division, National Cancer Center Research Institute.
D000818:Animals; D004247:DNA / Q000032:analysis / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage; D004252:DNA Mutational Analysis; D005609:Free Radicals; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D008214:Lymphocytes / Q000032:analysis; D051379:Mice; D009369:Neoplasms / Q000209:etiology*; D009374:Neoplasms, Experimental / Q000209:etiology; D010100:Oxygen / Q000009:adverse effects*; D051381:Rats
D005609:Free Radicals; C024829:8-hydroxyguanine; D006147:Guanine; D004247:DNA; D010100:Oxygen