Halliwell B
Department of Biochemistry, National University of Singapore, Kent Ridge Crescent, Singapore 119260, Singapore.
Mutat Res. 1999 Jul 15;443(1-2):37-52. doi: 10.1016/s1383-5742(99)00009-5.
Humans are exposed to many carcinogens, but the most significant may be the reactive species derived from metabolism of oxygen and nitrogen. Nitric oxide seems unlikely to damage DNA directly, but nitrous acid produces deamination and peroxynitrite leads to both deamination and nitration. Scavenging of reactive nitrogen species generated in the stomach may be an important role of flavonoids, flavonoids and other plant-derived phenolic compounds. Different reactive oxygen species produce different patterns of damage to DNA bases, e.g., such patterns have been used to implicate hydroxyl radical as the ultimate agent in H(2)O(2)-induced DNA damage. Levels of steady-state DNA damage in vivo are consistent with the concept that such damage is a major contributor to the age-related development of cancer and so such damage can be used as a biomarker to study the effects of diet or dietary supplements on risk of cancer development, provided that reliable assays are available. Methodological questions addressed in this article include the validity of measuring 8-hydroxydeoxyguanosine (8OHdG) in cellular DNA or in urine as a biomarker of DNA damage, the extent of artifact formation during analysis of oxidative DNA damage by gas chromatography-mass spectrometry and the levels of oxidative damage in mitochondrial DNA.
人类会接触到多种致癌物,但最重要的可能是源自氧和氮代谢的活性物质。一氧化氮似乎不太可能直接损伤DNA,但亚硝酸会导致脱氨作用,而过氧亚硝酸根会导致脱氨和硝化作用。清除胃中产生的活性氮物质可能是类黄酮、黄酮类化合物及其他植物来源的酚类化合物的重要作用。不同的活性氧物质对DNA碱基造成不同的损伤模式,例如,这些模式已被用于表明羟基自由基是H₂O₂诱导的DNA损伤中的最终作用因子。体内稳态DNA损伤水平与这样一种概念相符,即这种损伤是与年龄相关的癌症发展的主要促成因素,因此,只要有可靠的检测方法,这种损伤就可以用作生物标志物来研究饮食或膳食补充剂对癌症发生风险的影响。本文讨论的方法学问题包括在细胞DNA或尿液中测量8-羟基脱氧鸟苷(8OHdG)作为DNA损伤生物标志物的有效性、气相色谱-质谱法分析氧化性DNA损伤过程中假象形成的程度以及线粒体DNA中的氧化损伤水平。