Detection of 1,N-6-ethenodeoxyadenosine and 3,N-4-ethenodeoxycytidine by immunoaffinity/P-32-postlabelling in liver and lung DNA of mice treated with ethyl carbamate (urethane) or its metabolites
Detection of 1,N-6-ethenodeoxyadenosine and 3,N-4-ethenodeoxycytidine by immunoaffinity/P-32-postlabelling in liver and lung DNA of mice treated with ethyl carbamate (urethane) or its metabolites
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DOI：
10.1093/carcin/17.8.1711
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发表时间：
1996-08-01
期刊：
影响因子：
4.7
通讯作者：
Bartsch, H
中科院分区：
文献类型：
--
作者：
Fernando, RC;Nair, J;Bartsch, H
化学致癌物氨基甲酸乙酯本文研究了12日龄和成年CD-1、B_6C_3F_1、C_3H/HeJ和C_57BL/6 J小鼠肝和肺DNA中氨基甲酸乙酯（EC）及其代谢产物乙烯基氨基甲酸酯（VC）和乙烯基氨基甲酸酯环氧化物（VCO）形成乙烯碱基的能力。（β-dA）和3，N-3-乙烯脱氧胞苷通过免疫亲和层析/P-32-后标记技术定量测定（BdC）。在来自肝和肺的未处理对照DNA样品中检测到2-15个加合物/10（9）个亲本核苷酸的范围内的两种乙烯并加合物。57和78 μ dA/10（9）dA和28、42和42 μ dC/10（9）dC在CD-1、C3 H/HeJ和C57 BL/6 J小鼠的肝DNA中分别检测到了100个（重复分析的平均值），在这些VC处理的小鼠的肺DNA中分别检测到了87、49和58个（10（9）dA）和64、39和43在相似的给药方案下，B6 C3 F1小鼠体内检测到较低水平的乙烯加合物，成年小鼠经EC处理后，在肝和肺中也形成乙烯-DNA加合物，但其水平比VC低3倍，在12天大的C3 H/HeJ和C57 BL/6 J小鼠中，单次接受250 nmol/g体重VC处理后，肝脏DNA中检测到的乙烯加合物水平比成人高2至3倍，这表明幼年动物更容易形成加合物，成人CD-1中加合物形成的综合分析，较高剂量的C3 H/HeJ和C57 BL/6 J小鼠显示乙烯加合物形成的统计学显著增加，顺序为EC > VC。结果表明，EC及其活化的中间体与肝脏和肺DNA结合形成epsilon dA和epsilon dC，DNA结合的差异进一步支持了EC代谢活化为VC的假设，初步数据还表明，背景水平epsilon dA和epsilon dC在DNA中受到动物饮食类型的影响。
The capacity of the chemical carcinogen ethyl carbamate (EC, urethane) and its metabolites vinyl carbamate (VC) and vinyl carbamate epoxide (VCO) to form ethenobases was studied in liver and lung DNA of 12-day-old and adult CD-1, B6C3F1, C3H/HeJ and C57BL/6J mice, Following single and multiple doses of EC, VC or VCO, the formation of 1,N-6-ethenodeoxyadenosine (epsilon dA) and 3,N-3-ethenodeoxycytidine (epsilon dC) was quantified by an immunoaffinity chromatography/P-32-postlabelling technique, Both etheno adducts were detected in untreated control DNA samples from liver and lung in the range of 2-15 adducts/10(9) parent nucleotides, Following five repeated injections of 250 or 280 nmol/g body wt VC to adult mice, 51, 57 and 78 epsilon dA/10(9) dA and 28, 42 and 42 epsilon dC/10(9) dC (means of duplicate analyses) were detected in liver DNA of CD-1, C3H/HeJ and C57BL/6J mice respectively, In lung DNA of these VC-treated mice, the levels were 87, 49 and 58 (epsilon dA/10(9) dA) and 64, 39 and 43 (epsilon dC/10(9) dC) respectively, Under similar dose regimens, lower levels of etheno adducts were detected in B6C3F1 mice, Etheno-DNA adducts were also formed in liver and lung upon treatment with EC in adult mice, but at 3-fold lower levels as compared with VC, In 12-day-old C3H/HeJ and C57BL/6J mice, 2- to 3-fold higher etheno adduct levels were detected in liver DNA, when compared with adults, upon a single treatment with 250 nmol/g body wt VC, suggesting that young animals are more susceptible to adduct formation, Combined analysis of adduct formation in adult CD-1, C3H/HeJ and C57BL/6J mice at the higher dose showed a statistically significant increase in etheno adduct formation in the order EC > VC. The results demonstrate that EC and its activated intermediates bind to liver and lung DNA to form epsilon dA and epsilon dC, and the differences in DNA binding further support the hypothesis that metabolic activation of EC to VC is involved, Preliminary data also suggest that background levels of epsilon dA and epsilon dC in DNA are affected by the type of diet given to the animals.