FORMATION OF RIBONUCLEOTIDES IN DNA MODIFIED BY OXIDATIVE DAMAGE INVITRO AND INVIVO - CHARACTERIZATION BY P-32 POSTLABELING
FORMATION OF RIBONUCLEOTIDES IN DNA MODIFIED BY OXIDATIVE DAMAGE INVITRO AND INVIVO - CHARACTERIZATION BY P-32 POSTLABELING
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DOI：
10.1016/0921-8734(92)90038-q
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发表时间：
1992-09-01
期刊：
影响因子：
--
通讯作者：
RANDERATH, E
中科院分区：
文献类型：
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作者：
RANDERATH, K;REDDY, R;RANDERATH, E
Fe2+与H2O2相互作用产生氧自由基。 （芬顿反应）能够与 DNA 碱基发生反应，可能诱发诱变前和致癌前病变。通过此类反应在DNA中形成的产物已被表征为胞嘧啶、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开环衍生物。如 P-32 后标记所示，在 Fenton 反应条件下孵育 DNA 会在 DNA 中产生额外的氧化产物，通过氧化 DNA 的酶水解、P-32 后标记和具有真实标记的多个系统中的共色谱，将其表征为假定的核糖核苷。 DNA中这些产物的形成因反应混合物中L-抗坏血酸的存在而增强，并且它们的总量与主要DNA氧化产物8-羟基-2'-脱氧鸟苷的总量相似。用次氮基三乙酸铁（一种肾致癌物）治疗的雄性大鼠的肾脏 DNA 中也会形成核糖核苷鸟苷。据推测，核糖核苷酸会改变 DNA 的构象和功能，因此它们在 DNA 中的存在可能会对健康产生不利影响。
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 P-32-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, P-32-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.