DNA-PURINE METHYLATION IN HEPATIC CHROMATIN FOLLOWING EXPOSURE TO DIMETHYLNITROSAMINE OR METHYLNITROSOUREA
DNA-PURINE METHYLATION IN HEPATIC CHROMATIN FOLLOWING EXPOSURE TO DIMETHYLNITROSAMINE OR METHYLNITROSOUREA
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DOI：
10.1016/0006-2952(84)90312-5
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发表时间：
1984-01-01
影响因子：
5.8
通讯作者：
GOODMAN, JI
中科院分区：
文献类型：
--
作者：
FAUSTMANWATTS, EM;GOODMAN, JI
这些研究旨在分析体内暴露于致癌烷化剂二甲基亚硝胺(DMN)或甲基亚硝脲(MNU)后，肝染色质中DNA嘌呤甲基化的模式。雄性SD大鼠经胃管暴露于[14C]DMN(8微克/毫摩尔，1.0微克/微克分子)或[~3H]MNU(15微克/微克分子，每100克10微克Ci/微克分子)。经DNase II消化和氯化镁沉淀，将肝染色质分成具有模板活性常染色质(S2)和模板抑制异染色质(P2)特征的部分。在插管后24小时，用等压高效液相色谱系统鉴定特定的DNA嘌呤。总染色质DNA与异染色质DNA在两种致癌物质作用后24 h，均观察到7-甲基鸟嘌呤、O6-甲基鸟嘌呤、1-甲基腺嘌呤和3-甲基腺嘌呤的烷基化模式。这些评估是在致癌物暴露后进行的，致癌物暴露在常染色质与异染色质DNA的烷基化程度上产生了最大的数量差异。在总染色质和异染色质中观察到类似的DNA嘌呤烷基化模式。一旦产生了活性物质并获得了染色质DNA，在基因组的不同区域就会产生类似的DNA-嘌呤烷基化模式。
These investigations were designed to analyze the patterns of DNA purine methylation in hepatic chromatin following in vivo exposure to the carcinogenic alkylating agents dimethylnitrosamine (DMN) or methylnitrosourea (MNU). Male Sprague-Dawley rats were exposed to [14C]DMN (8 .mu.mol, 1.0 .mu.Ci/.mu.mol per 100g) or [3H]MNU (15 .mu.moles, 10 .mu.Ci/.mu.mol per 100 g) via gastric intubation. Hepatic chromatin was fractionated into portions having characteristics of template-active euchromatin (S2) and template-repressed heterochromatin (P2) by digestion with DNase II followed by MgCl2 precipitation. Specific DNA purines were identified at 24 h post-intubation using an isocratic high pressure liquid chromatographic system. A qualitatively similar pattern of 7-methylguanine, O6-methylguanine, 1-methyladenine and 3-methyladenine alkylation was observed in DNA from total chromatin vs. heterochromatin at 24 h following exposure to either carcinogen. These assessments were made at times following carcinogen exposure which produced maximal quantitative differences in alkylation of euchromatin vs. heterochromatin DNA. Similar patterns of DNA purine alkylation were observed in total chromatin and heterochromatin. Once the reactive species is generated and access to chromatin DNA occurs, a similar pattern of DNA-purine alkylation is produced in different regions of the genome.