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用碱性洗脱技术评估经N-亚硝基二烷基胺处理的大鼠和仓鼠的肝脏、肾脏及肺中的DNA损伤情况。

Evaluation of DNA damage by the alkaline elution technique in liver, kidneys and lungs of rats and hamsters treated with N-nitrosodialkylamines.

作者信息

Barbin A, Béréziat J C, Bartsch H

出版信息

Carcinogenesis. 1983;4(5):541-5. doi: 10.1093/carcin/4.5.541.

DOI:10.1093/carcin/4.5.541
PMID:6850984
Abstract

Induction of single-strand breaks in the DNA of three organs of BD-VI rats and Syrian golden hamsters was examined 4 h after a single i.p. dose of N-nitrosodimethylamine (DMN) or N-nitrosodiethylamine (DEN). Damage was monitored in vivo by the alkaline elution method, in which DNA is dosed fluorometrically. DNA damage was induced by DMN in the liver and kidneys of rats and in the liver and lungs of hamsters, and by DEN in rat and hamster liver. High doses of the hepatocarcinogen and hepatotoxic compound carbon tetrachloride, did not induce DNA damage in rat liver. A correspondence between DNA fragmentation (our study) and tumour induction (reported in the literature) was found in the following organs: rat and hamster liver (DMN, DEN), rat kidney (DMN), rat lung (DMN, DEN), hamster kidney (DMN, DEN). In contrast, no such correlation was observed in rat kidney and hamster lung following DEN-treatment and in hamster lung following DMN-treatment. Thus, the in vivo alkaline elution assay would appear to be most useful for detecting DNA damage by chemicals that are activated metabolically in the liver and that bind to hepatic DNA.

摘要

在腹腔注射单剂量的N-亚硝基二甲胺(DMN)或N-亚硝基二乙胺(DEN)4小时后,检测BD-VI大鼠和叙利亚金仓鼠三个器官DNA中的单链断裂情况。采用碱性洗脱法在体内监测损伤,该方法通过荧光测定法对DNA进行定量。DMN可诱导大鼠肝脏和肾脏以及仓鼠肝脏和肺脏中的DNA损伤,DEN可诱导大鼠和仓鼠肝脏中的DNA损伤。高剂量的肝癌致癌物和肝毒性化合物四氯化碳未诱导大鼠肝脏中的DNA损伤。在以下器官中发现了DNA片段化(本研究)与肿瘤诱导(文献报道)之间的对应关系:大鼠和仓鼠肝脏(DMN、DEN)、大鼠肾脏(DMN)、大鼠肺脏(DMN、DEN)、仓鼠肾脏(DMN、DEN)。相比之下,在DEN处理后的大鼠肾脏和仓鼠肺脏以及DMN处理后的仓鼠肺脏中未观察到这种相关性。因此,体内碱性洗脱试验似乎最适用于检测在肝脏中经代谢活化并与肝脏DNA结合的化学物质所导致的DNA损伤。

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