DNA METHYLATION AND METHYLASE LEVELS IN NORMAL AND MALIGNANT MOUSE HEPATIC TISSUES

DNA METHYLATION AND METHYLASE LEVELS IN NORMAL AND MALIGNANT MOUSE HEPATIC TISSUES
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DOI:
10.1093/carcin/2.9.873
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发表时间:
1981-01-01
期刊:
影响因子:
4.7
通讯作者:
BECKER, FF
BECKER, FF
中科院分区:
医学2区
文献类型:
--
作者:
LAPEYRE, JN;WALKER, MS;BECKER, FF

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通过测定核DNA中5-甲基胞嘧啶的含量,研究了3株小鼠正常肝脏和化学诱导或自发原发性肝细胞癌(PHC)的DNA甲基化状态。与背景和正常肝脏样本相比,C3H小鼠的自发性肿瘤以及C57Bl和B6C3小鼠的乙酰氨基芴、氯丹或3''-甲基-4-二甲氨基偶氮苯诱导的肿瘤的DNA甲基化程度较低。在C3H小鼠中检测了正常肝脏、背景肝脏和PHC的DNA甲基化酶活性,以确定所观察到的基因组甲基化是否与该酶的功能障碍有关,并将其与这些组织中的DNA合成率进行了比较。与背景相比,肿瘤细胞核的DNA甲基化酶水平升高。在该系统的肿瘤基因组中发现的低甲基化不是由于该酶的失活,也不是由于该酶的活性相对于肿瘤中对从头合成DNA甲基化的需求而显着缺乏。
The status of DNA methylation, as measured by the 5-methylcytosine content of nuclear DNA, was examined in normal livers and in chemically induced or spontaneous primary hepatocellular carcinoma (PHC) arising in 3 strains of mice. The DNA from spontaneous tumors of genetic origin in C3H mice and also from acetylaminofluorene, chlordane or 3''-methyl-4-dimethylaminoazobenzene-induced tumors in C57Bl and B6C3 mice was undermethylated compared to the levels in background and normal liver samples. The DNA methylase activities from normal liver, background liver and PHC were assayed in C3H mice to determine whether the observed genomic undermethylation is related to a dysfunction of this enzyme and were compared to the rates of DNA synthesis in these tissues. DNA methylase levels from tumor nuclei were elevated compared to background. The undermethylation found in the tumor genomes of this system is not due to inactivation nor a significant deficiency of the activity of this enzyme relative to the demand in tumors for methylation of de novo synthesized DNA.