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外文期刊>Teratogenesis, carcinogenesis, and mutagenesis
>Comparison of DNA alkylation, fragmentation, and repair in maternal and fetal tissues of pregnant rats treated with a single dose of ethyl methanesulfonate, ethyl‐N‐nitrosourea, N‐nitrosodiethylamine, and methyl‐N‐nitrosourea
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Comparison of DNA alkylation, fragmentation, and repair in maternal and fetal tissues of pregnant rats treated with a single dose of ethyl methanesulfonate, ethyl‐N‐nitrosourea, N‐nitrosodiethylamine, and methyl‐N‐nitrosourea
AbstractThe occurrence and persistence of DNA damage, as detected by the alkaline elution technique, have been studied in some tissues of both fetal and adult Sprague‐Dawley rats (18th day of gestation) after administration of a single equimolar dose (0.5 mmol/kg) of ethyl methanesulfonate (EMS), N‐ethyl‐N‐nitrosourea (ENU), N‐nitrosodiethylamine (NDEA), and N‐methyl‐N‐nitrosourea (MNU). EMS, ENU, and MNU, injected intravenously, produced a statistically significant increase of DNA elution rate, which is considered indicative of DNA fragmentation, in both maternal and fetal liver, kidney, and brain. NDEA, introduced by gastric gavage, induced DNA breaks in both liver and kidney of dams, but only in the liver of fetuses. The frequency of DNA lesions was found to vary with the four alkylating agents and in the three organs tested, to exhibit a different time course, and usually to be higher in maternal than in fetal tissues. Results provided by the concomitant determination of DNA binding levels demonstrated a satisfactory correlation with the amounts of DNA fragmentation. In contrast, the values of both these parameters did not show any positive correlation with the different susceptibility of the three organs to tumor induction. In conclusion, these findings suggest that when a compound is not available in radiolabeled form, measurement of DNA fragmentation may represent a useful alternative to the determination of DNA binding level in order to obtain information on the distribution of its reactive species in maternal an
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机译:摘要 采用碱性洗脱技术对Sprague-Dawley大鼠(妊娠第18天)给予单次等摩尔剂量(0.5 mmol/kg)甲磺酸乙酯(EMS)、N-乙基-N-亚硝基脲(ENU)、N-亚硝基二乙胺(NDEA)和N-甲基-N-亚硝基脲(MNU)后,在胎儿和成年Sprague-Dawley大鼠的一些组织中检测DNA损伤的发生和持续性进行了研究。静脉注射的 EMS、ENU 和 MNU 在母体和胎儿的肝脏、肾脏和大脑中产生了 DNA 洗脱率的统计学显着增加,这被认为是 DNA 片段化的指示。由胃灌胃引入的NDEA在水坝的肝脏和肾脏中引起DNA断裂,但仅在胎儿的肝脏中引起DNA断裂。发现DNA损伤的频率随四种烷化剂和测试的三个器官而变化,表现出不同的时间过程,并且通常在母体组织中高于胎儿组织。同时测定 DNA 结合水平所提供的结果表明,与 DNA 片段化量具有令人满意的相关性。相比之下,这两个参数的值与三个器官对肿瘤诱导的不同易感性没有显示出任何正相关。总之,这些发现表明,当一种化合物不能以放射性标记形式存在时,DNA片段的测量可能代表了测定DNA结合水平的有用替代方法,以获得有关其反应性物质在母体中分布的信息。
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