Long-lived mutagenic radicals induced in mammalian cells by ionizing radiation are mainly localized to proteins
Long-lived mutagenic radicals induced in mammalian cells by ionizing radiation are mainly localized to proteins
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DOI：
10.1667/rr3015
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发表时间：
2003-07-01
影响因子：
3.4
通讯作者：
Miyazaki, T
中科院分区：
文献类型：
--
作者：
Kumagai, J;Masui, K;Miyazaki, T
我们提供的证据表明，电离辐射产生的长寿命自由基在哺乳动物细胞中具有高度诱变性和转化性。维生素C或表没食子儿茶素-3-O-没食子酸酯（EGCG）可有效清除长寿命的自由基。长寿命的自由基不参与致死或诱导染色体畸变。我们现在报告的实验结果，定义了DNA和蛋白质中长寿命自由基的相对数量，并确定了主要的蛋白质自由基为亚磺酰基自由基（R-CH 2-S-O-）。为了使这些分配，产量的长寿命的自由基在γ射线照射鲑鱼精子DNA和白蛋白进行了比较ESR。对辐照叙利亚仓鼠胚胎（SHE）细胞产生的长寿命自由基的ESR谱进行了精确分析，并与密度泛函理论计算得到的ESR参数进行了比较。长寿命的自由基产率为99.8%的蛋白质。我们还发现了一种新的长寿命自由基的H-加苯丙氨酸自由基。虽然我们的证据并不排除辐射产生的低水平长寿命自由基的重要生物后果的可能性，但它暗示蛋白质中的自由基在电离辐射的遗传效应中发挥关键作用。我们认为，这些新的自由基，无论他们居住在哪里，需要考虑在辐射的生物后遗症的解释。(C)2003年，辐射研究协会。
We have provided evidence that long-lived radicals, produced by ionizing radiation, are highly mutagenic and transforming in mammalian cells. Long-lived radicals are scavenged effectively by vitamin C or by epigallocatechin-3-O-gallate (EGCG). Long-lived radicals are not involved in lethality or in the induction of chromosome aberrations. We now report the results of experiments that define the relative amounts of long-lived radicals in DNA and proteins and identify the major protein radicals as sulfinyl radicals (R-CH2-S-O-.). To make these assignments, yields of long-lived radicals in gamma-irradiated salmon sperm DNA and albumin were compared by ESR. ESR spectra of long-lived radicals produced in irradiated Syrian hamster embryo (SHE) cells were analyzed precisely and compared with ESR parameters obtained by density functional theory calculations. Long-lived radicals yields of 99.8% were produced in proteins. We also identified a new type of long-lived radical as H-added phenylalanine radicals. While our evidence does not rule out the possibility of important biological consequences of the low-level long-lived radicals created by radiation, it implicates radicals in proteins as playing a key role in genetic effects of ionizing radiation. We suggest that these novel radicals, wherever they reside, need to be considered in explanations of biological sequela of radiation. (C) 2003 by Radiation Research Society.