5-Hydroxymethyl Uracil: A Product of Ionizing Radiation and Tritium Transmutation Formed in DNA-猫眼课题宝

5-羟甲基尿嘧啶：DNA 中电离辐射和氚转化的产物

DOI：

10.1007/978-1-4684-5269-3_36

发表时间：

1986

期刊：

Mutation research

影响因子：

通讯作者：

中科院分区：

文献类型：

作者：

K. Frenkel;A. Cummings;G. Teebor

电离辐射的致突变性和致癌性被认为是其引起的DNA损伤的结果（1）。这种DNA损伤包括单链和双链断裂、DNA-蛋白质交联、碱基丢失与AP位点的形成和碱基的化学修饰（2-6）。在这些碱基中，胸腺嘧啶部分似乎最容易受到电离辐射的修饰作用（7，8）。研究最多的衍生物之一，通过电离辐射作用形成，胸腺嘧啶乙二醇（TG），是通过氧化胸腺嘧啶的5，6-双键形成的（图1）（2，9-13）。TG易于被放射性衍生的羟基自由基进一步氧化。它导致开环并形成不稳定的N '-甲酰基-N-异丙基脲（FPU），其断裂或环化并成为5-羟基-5-甲基乙内酰脲（HMH）（9，10，14）。另一种胸腺嘧啶衍生物5-羟甲基尿嘧啶（HMUra）是通过氧化胸腺嘧啶的甲基形成的（图1）（15-17）。与TG相反，HMUra化学稳定（18）。因此，HMUra有可能作为电离辐射暴露的标志物，其方式与环丁烷嘧啶二聚体成为UV辐射暴露的标志物相同。

The mutagenic and carcinogenic properties of ionizing radiation are thought to be a consequence of DNA damage it causes (1). Such DNA damage includes single- and double-strand breaks, DNA-protein crosslinks, base loss with formation of AP sites and chemical modification of bases (2–6). Among the bases, the thymine moiety appears to be the most susceptible to the modifying effects of ionizing radiation (7, 8). One of the most studied derivatives formed through the action of ionizing radiation, thymine glycol (TG), is formed by the oxidation of the 5,6-double bond of thymine (Figure 1) (2, 9-13). TG is susceptible to further oxidation by radiogenically-derived hydroxyl radicals. It leads to the opening of the ring and formation of an unstable N’-formyl-N-pyruvyl urea (FPU) which either fragments or cyclizes and becomes 5-hydroxy-5-methyl hydantoin (HMH) (9, 10, 14). The other thymine derivative, 5-hydroxymethyl uracil (HMUra), is formed by oxidation of the methyl group of thymine (Figure 1) (15–17). In contrast to TG, HMUra is chemically stable (18). Therefore, it is possible that HMUra will serve as a marker of exposure to ionizing radiation in the same way as cyclobutane pyrimidine dimers became markers of exposure to UV radiation.

Ionizing radiation and tritium transmutation both cause formation of 5-hydroxymethyl-2'-deoxyuridine in cellular DNA.