Randerath K, Reddy R, Danna T F, Watson W P, Crane A E, Randerath E
Department of Pharmacology, Baylor College of Medicine, Houston, TX 77030.
Mutat Res. 1992 Sep;275(3-6):355-66. doi: 10.1016/0921-8734(92)90038-q.
Oxygen free radicals generated by the interaction of Fe2+ and H2O2 (Fenton reaction) are capable of reacting with DNA bases, which may induce premutagenic and precarcinogenic lesions. Products formed in DNA by such reactions have been characterized as hydroxylated derivatives of cytosine, thymine, adenine, and guanine and imidazole ring-opened derivatives of adenine and guanine. As shown here by 32P-postlabeling, incubation of DNA under Fenton reaction conditions gave rise to additional oxidation products in DNA that were characterized as putative ribonucleosides by enzymatic hydrolysis of the oxidized DNA, 32P-postlabeling, and co-chromatography in multiple systems with authentic markers. Formation of these products in DNA was enhanced by the presence of L-ascorbic acid in the reaction mixtures and their total amounts were similar to those of the major DNA oxidation product, 8-hydroxy-2'-deoxyguanosine. The ribonucleoside guanosine was also formed in kidney DNA of male rats treated with ferric nitrilotriacetate, a renal carcinogen. It is postulated that ribonucleotides alter conformation and function of DNA and thus their presence in DNA may lead to adverse health effects.
由Fe2+与H2O2相互作用产生的氧自由基（芬顿反应）能够与DNA碱基发生反应，这可能会诱导产生致突变前和致癌前的损伤。此类反应在DNA中形成的产物已被鉴定为胞嘧啶、胸腺嘧啶、腺嘌呤和鸟嘌呤的羟基化衍生物以及腺嘌呤和鸟嘌呤的咪唑环开环衍生物。如本文通过32P后标记法所示，在芬顿反应条件下孵育DNA会产生额外的DNA氧化产物，通过对氧化后的DNA进行酶水解、32P后标记以及与标准标记物在多个系统中进行共色谱分析，这些产物被鉴定为推定的核糖核苷。反应混合物中L-抗坏血酸的存在会增强这些产物在DNA中的形成，并且它们的总量与主要的DNA氧化产物8-羟基-2'-脱氧鸟苷的总量相似。用肾致癌物次氮基三乙酸铁处理的雄性大鼠的肾脏DNA中也形成了核糖核苷鸟苷。据推测，核糖核苷酸会改变DNA的构象和功能，因此它们在DNA中的存在可能会导致不良的健康影响。
