Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl, and 2-acetylaminophenanthrene.
Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl, and 2-acetylaminophenanthrene.
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用 2-乙酰氨基芴、4-乙酰氨基联苯和 2-乙酰氨基菲的 N-羟基衍生物处理的大鼠肝脏中 DNA 加合物的形成和去除。
DOI：
10.1093/carcin/5.3.343
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发表时间：
1984
期刊：
影响因子：
4.7
通讯作者：
Dighe,NR
中科院分区：
文献类型：
--
作者：
Gupta,RC;Dighe,NR
本文研究了单次注射两种致癌物N-羟基-2-乙酰氨基芴（N-OH-AAF）和N-羟基-4-乙酰氨基联苯（N-OH-AABP）及一种非致癌物N-羟基-2-乙酰氨基菲（N-OH-AAP）后0.5h、1.5h、4 h、24 h、9d和29 d肝DNA加合物的形成和清除。使用先前描述的32 P-后标记测定，分别在约1.5 h、0.5 h和24 h观察到这些化合物的最大DNA结合。除了形成三个已知的C8-和N2-乙酰化和C8-脱乙酰化鸟嘌呤衍生物和几个次要的未知加合物与N-OH-AAF，一组四个新的主要加合物也被检测到。在前4小时内，这些加合物占总加合物的约50%。在24 h、9 d和29 d后，三种已知加合物分别为1.5 h值的58%、16%和6%，而大部分（>84%）的新的主要加合物在24 h内从DNA中除去，并且在9 d后仅以痕量存在。N-OH-AABP形成几个未知的次要加合物，除了一个主要的C8-脱乙酰化和两个次要的C8-和N2-乙酰化鸟嘌呤衍生物;只有C8-脱乙酰化和N2-乙酰化加合物在29 d后被检测到。在N-OH-AAP的情况下，两个主要的和几个次要的加合物被检测到，其中大部分被发现是脱乙酰化的，和多达60%的加合物在24小时测量仍然存在9天的治疗后。这些数据表明，某些DNA加合物被迅速修复，而另一些则持续很长时间。
Formation and removal of hepatic DNA adducts was studied in male Sprague-Dawley rats following single injections of two hepatocarcinogens, N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and a nonhepatocarcinogen, N-hydroxy-2-acetylaminophenanthrene (N-OH-AAP) at 0.5 h, 1.5 h, 4 h, 24 h, 9 d and 29 d. Using a previously described32P-postlabeling assay, maximal DNA binding of these compounds was observed at approximately 1.5 h, 0.5 h and 24 h, respectively. In addition to the formation of three already known C8- and N2-acetylated and C8-deacetyiated guanine derivatives and several minor unknown adducts with N-OH-AAF, a set of four new major adducts was also detected. These comprised ∼50% of the total adducts during the first 4 h. The three known adducts amounted to 58, 16 and 6% of the 1.5-h value after 24 h, 9 d and 29 d, respectively, while the bulk (>84%) of the new major adducts were removed from the DNA within 24 h and found only in traces after 9 d. N-OH-AABP formed several unknown minor adducts, in addition to the one major C8-deacetylated and two minor C8- and N2-acetylated guanine derivatives; only the C8-deacetylated and N2-acetylated adducts were detected after 29 d. In the case of N-OH-AAP, two major and several minor adducts were detected, most of which were found to be deacetylated, and as much as 60% of the adducts measured at 24 h were still present after 9 d treatment. These data indicte that certain DNA adducts are repaired rapidly, while others persist for long periods.