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给予致癌剂量的二甲基亚硝胺后,叙利亚金仓鼠各种组织的脱氧核糖核酸中的甲基化嘌呤。

Methylated purines in the deoxyribonucleic acid of various Syrian-golden-hamster tissues after administration of a hepatocarcinogenic dose of dimethylnitrosamine.

作者信息

Margison G P, Margison J M, Montesano R

出版信息

Biochem J. 1976 Sep 1;157(3):627-34. doi: 10.1042/bj1570627.

Abstract
  1. DNA was extracted from livers, kidneys and lungs of Syrian golden hamsters at various times (up to 96h) after injection of a hepatocarcinogenic dose of [14C]dimethylnitrosamine. Purine bases were released from the DNA by mild acid hydrolysis and separated by Sephadex G-10 chromatography. 2. At 7h after dimethylnitrosamine administration liver DNA was alkylated to the greatest extent, followed by that of lung and kidney, the values for which were 8 and 3% respectively of those for liver. 3. The O6-methylguanine/7-methylguanine ratios were initially the same in all three organs and in the liver DNA of rats under similar conditions of dose. 4. O6-Methylguanine was the most persistent alkylated purine in all three hamster tissues. There was evidence for excision of 7-methyl-guanine, the highest activity for this being present in the liver. 5. Detectable amounts of the minor products 3-methyladenine, 1-methyladenine, 3-methylguanine and 7-methyladenine were present in most hamster tissues, and their individual rates of loss from liver DNA were determined. 6. Ring-labelling of the normal purines in DNA was highest in the liver, followed closely by the lung (80% of that in liver) whereas the kidney had very low incorporation (3% of that in liver). 7. The results are discussed with respect to the hepatotoxicity of dimethylnitrosamine, the miscoding potential of the various alkylation products and the induction of liver tumours in hamsters.
摘要
  1. 在给叙利亚金仓鼠注射致癌剂量的[14C]二甲基亚硝胺后的不同时间(最长96小时),从其肝脏、肾脏和肺中提取DNA。通过温和酸水解从DNA中释放嘌呤碱,并通过葡聚糖凝胶G - 10色谱法进行分离。2. 二甲基亚硝胺给药后7小时,肝脏DNA的烷基化程度最高,其次是肺和肾脏,肺和肾脏的烷基化值分别为肝脏的8%和3%。3. 在所有三个器官以及在相似剂量条件下大鼠的肝脏DNA中,O6 - 甲基鸟嘌呤/7 - 甲基鸟嘌呤的比率最初是相同的。4. O6 - 甲基鸟嘌呤是所有三种仓鼠组织中最持久的烷基化嘌呤。有证据表明7 - 甲基鸟嘌呤被切除,肝脏中这种切除活性最高。5. 在大多数仓鼠组织中存在可检测量的次要产物3 - 甲基腺嘌呤、1 - 甲基腺嘌呤、3 - 甲基鸟嘌呤和7 - 甲基腺嘌呤,并测定了它们从肝脏DNA中各自的损失率。6. DNA中正常嘌呤的环标记在肝脏中最高,其次是肺(为肝脏的80%),而肾脏的掺入率非常低(为肝脏的3%)。7. 讨论了关于二甲基亚硝胺的肝毒性、各种烷基化产物的错配潜力以及仓鼠肝脏肿瘤诱导的结果。

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