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人类肿瘤细胞系和新鲜儿科肿瘤外植体中可变的5-甲基胞嘧啶水平。

Variable 5-methylcytosine levels in human tumor cell lines and fresh pediatric tumor explants.

作者信息

Flatau E, Bogenmann E, Jones P A

出版信息

Cancer Res. 1983 Oct;43(10):4901-5.

PMID:6883340
Abstract

DNA methylation was measured in human tumor cell lines and freshly explanted pediatric tumors by [3H]uridine labeling followed by DNA hydrolysis and high-performance liquid chromatography. The percentage of cytosine residues modified to 5-methylcytosine in 4 cell lines derived from pediatric tumors was increased or similar to the levels of 3.45% found in two strains of diploid human fibroblasts. However, a fibrosarcoma line derived from an adult (HT1080) contained decreased levels of 5-methylcytosine. Four low-passage retinoblastomas had uniform 5-methylcytosine levels of approximately 3.9%, whereas the levels of the modified base in two freshly explanted rhabdomyosarcomas, one Wilms' tumor, and one medulloblastoma were 3.39, 3.56, and 3.45%, respectively. Two neuroblastomas had substantially lower levels (2.63 to 2.83%) of 5-methylcytosine in their DNAs compared to the retinoblastomas, which are also derived from neural tissue. The results show that while tumors of the same histological type had similar 5-methylcytosine values, discrepancies existed between values obtained for fresh tumors and their corresponding cell lines. Tumor cell lines may therefore be inadequate models for studies on the relationship between DNA methylation and cancer. The results also indicate that generalized statements on DNA methylation levels in pediatric tumors cannot be made, although substantial variations may occur between different tumors types.

摘要

通过[3H]尿苷标记,随后进行DNA水解和高效液相色谱法,测定了人肿瘤细胞系和新切除的儿科肿瘤中的DNA甲基化。来自儿科肿瘤的4种细胞系中,修饰为5-甲基胞嘧啶的胞嘧啶残基百分比增加或与在两株二倍体人成纤维细胞中发现的3.45%的水平相似。然而,一株源自成人的纤维肉瘤细胞系(HT1080)中5-甲基胞嘧啶水平降低。4例低传代视网膜母细胞瘤的5-甲基胞嘧啶水平均一,约为3.9%,而在两个新切除的横纹肌肉瘤、1例肾母细胞瘤和1例髓母细胞瘤中,修饰碱基的水平分别为3.39%、3.56%和3.45%。与同样源自神经组织的视网膜母细胞瘤相比,两例神经母细胞瘤DNA中的5-甲基胞嘧啶水平显著较低(2.63%至2.83%)。结果表明,虽然相同组织学类型的肿瘤具有相似的5-甲基胞嘧啶值,但新鲜肿瘤及其相应细胞系获得的值之间存在差异。因此,肿瘤细胞系可能不是研究DNA甲基化与癌症关系的合适模型。结果还表明,尽管不同肿瘤类型之间可能存在显著差异,但不能对儿科肿瘤中的DNA甲基化水平做出一般性陈述。

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Variable 5-methylcytosine levels in human tumor cell lines and fresh pediatric tumor explants.人类肿瘤细胞系和新鲜儿科肿瘤外植体中可变的5-甲基胞嘧啶水平。
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