Induction of fragile sites by fluorodeoxyuridine and caffeine accompanies with misincorpolation of endogenous uridine nucleotide into DNA of feline fibroblasts.

Induction of fragile sites by fluorodeoxyuridine and caffeine accompanies with misincorpolation of endogenous uridine nucleotide into DNA of feline fibroblasts.
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氟脱氧尿苷和咖啡因诱导脆弱位点伴随着内源性尿苷核苷酸错误地掺入猫成纤维细胞的 DNA 中。

DOI:
10.1292/jvms.60.1293
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发表时间:
1998
期刊:
The Journal of veterinary medical science
影响因子:
--
通讯作者:
Y. Takamori
Y. Takamori
中科院分区:
--
文献类型:
--
作者:
K. Kubo;A. Shiomi;A. Asaeda;F. Ohashi;S. Matsuyama;H. Ide;Y. Takamori

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氟代脱氧尿苷是胸苷合成酶的一种抑制剂,已知会导致染色体脆性部位。药物治疗可能导致细胞内胸腺嘧啶核糖核酸池的剥夺,进而导致脱氧核酸池的严重失衡。虽然压力可能与叶酸敏感的脆性部位的诱导有关,但确切的机制仍有待研究。进行这项研究是为了测试脆性位点至少部分起源于无关联的尿嘧啶残基的可能性。用尿嘧啶-DNA N-糖基酶(UDG)处理后,可以用一种新的碱性位点检测方法来检测未关联的尿嘧啶残留物。经FUDR和咖啡因处理后,从猫成纤维细胞中提取的DNA中每10(4)个核苷酸中约检测到2.7个基本位点。通过在检测前用UDG消化DNA,观察到基本位点的数量显著增加。这些结果表明,猫成纤维细胞DNA中存在大量的尿嘧啶残基,这是导致染色体脆性部位的条件。
Fluorodeoxyuridine, an inhibitor of thymidylate synthetase, is known to induce chromosomal fragile sites. The drug treatment may cause deprivation of intracellular thymidine nucleotide pool followed by a serious imbalance of deoxynucleotide pool. Though the stress is probably related to the induction of folate-sensitive fragile sites, the exact mechanism is still to be investigated. The present study has been carried out to test the possibility that the fragile sites are originated, at least in part, from incorpolated uracil residues. The incorpolated uracil residue can be detected by a novel assay for abasic sites after treatment with uracil-DNA N-glycosylase (UDG). About 2.7 abasic sites per 10(4) nucleotides were detected in the DNA extracted from feline fibroblasts after the treatment with FUdR and caffeine. By digesting the DNA with UDG prior to the assay, significant increase in the number of abasic sites were observed. These results indicate that the large amount of uracil residues are present in the feline fibroblast DNA under the condition which induces chromosomal fragile sites.
DOI: 10.1128/mcb.23.23.8740-8750.2003
发表时间: 2003-12-01
影响因子: 5.3
作者:
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DOI: --
发表时间: 1983
期刊: The Journal of biological chemistry
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