Cadenas S, Barja G
Department of Animal Biology-II (Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain.
Free Radic Biol Med. 1999 Jun;26(11-12):1531-7. doi: 10.1016/s0891-5849(99)00019-2.
Free radical scavengers can protect against the genotoxicity induced by chemical carcinogens by decreasing oxidative damage. The protective effect of the antioxidants melatonin, resveratrol, vitamin E, butylated hydroxytoluene and 2-mercaptoethylamine, and the spin-trapping compound alpha-phenyl-N-tert-butyl nitrone (PBN) against oxidative DNA damage was studied in the kidney of rats treated with the kidney-specific carcinogen potassium bromate (KBrO3). KBrO3 was given to rats previously treated with melatonin, resveratrol, PBN, vitamin E, butylated hydroxytoluene, or 2-mercaptoethylamine. Oxidative damage to kidney DNA was estimated 6 hours afterwards by measuring 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo8dG) referred to deoxyguanosine (dG) by means of high performance liquid chromatography with electrochemical-coulometric and ultraviolet detection. Levels of oxo8dG in the renal genomic DNA significantly increased by more than 100% after the KBrO3 treatment. This increase was completely abolished by the treatment with resveratrol and was partially prevented by melatonin, PBN and vitamin E. Resveratrol and PBN also prevented the increase in relative kidney weight induced by KBrO3. These results show that various different antioxidants and a free radical trap, working in either the water-soluble or the lipid-soluble compartments, can prevent the oxidative DNA damage induced in the kidney by the carcinogen KBrO3.
自由基清除剂可通过减少氧化损伤来抵御化学致癌物诱导的遗传毒性。在经肾脏特异性致癌物溴酸钾（KBrO₃）处理的大鼠肾脏中，研究了抗氧化剂褪黑素、白藜芦醇、维生素E、丁基羟基甲苯和2-巯基乙胺以及自旋捕获化合物α-苯基-N-叔丁基硝酮（PBN）对氧化性DNA损伤的保护作用。给预先用褪黑素、白藜芦醇、PBN、维生素E、丁基羟基甲苯或2-巯基乙胺处理过的大鼠给予KBrO₃。6小时后，通过高效液相色谱结合电化学-库仑法和紫外检测，测量相对于脱氧鸟苷（dG）的8-氧代-7,8-二氢-2'-脱氧鸟苷（oxo8dG），来评估肾脏DNA的氧化损伤。KBrO₃处理后，肾脏基因组DNA中的oxo8dG水平显著增加了100%以上。白藜芦醇处理完全消除了这种增加，褪黑素、PBN和维生素E则部分预防了这种增加。白藜芦醇和PBN还预防了KBrO₃诱导的相对肾脏重量增加。这些结果表明，各种不同的抗氧化剂和一种自由基捕获剂，无论在水溶性还是脂溶性区室发挥作用，都可以预防致癌物KBrO₃在肾脏中诱导的氧化性DNA损伤。
