Antifolate-induced misincorporation of deoxyuridine monophosphate into DNA: inhibition of high molecular weight DNA synthesis in human lymphoblastoid cells.
Antifolate-induced misincorporation of deoxyuridine monophosphate into DNA: inhibition of high molecular weight DNA synthesis in human lymphoblastoid cells.
复制标题
抗叶酸诱导的脱氧尿苷单磷酸错误掺入 DNA：抑制人淋巴母细胞中高分子量 DNA 的合成。
DOI：
10.1073/pnas.78.2.917
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发表时间：
1981
影响因子：
11.1
通讯作者：
Brown,OE
中科院分区：
文献类型：
--
作者：
Sedwick,WD;Kutler,M;Brown,OE
在体外暴露的人淋巴母细胞系（WIL-2）的抗叶酸剂甲巯嘌呤（DIFFERENTIAL），随后加入外源性脱氧尿苷，导致细胞内积累的脱氧尿苷三磷酸（dUTP）和脱氧尿苷一磷酸（dUMP）的DNA。当新合成的DNA提取DDMP处理的细胞，已标记脱氧尿苷长达3分钟，大多数的DNA合成不大于4 S的碱性蔗糖梯度。相比之下，未用药物处理的细胞中新合成的碱稳定DNA的主要形式大于4S。当胸苷用于标记DDP处理的DNA时，在不存在外源性脱氧尿苷的情况下，DNA合成的异常进展、新合成的DNA的降解或两者均作为DDMP处理的延迟结果发生。未阐明抗叶酸剂诱导的dUMP错误掺入DNA的稳定性，很明显，抗叶酸剂可直接干扰药物处理细胞合成的DNA的质量和数量。
In vitro exposure of a human lymphoblastoid cell line (WIL-2) to the antifolate metoprine (DDMP), when followed by the addition of exogenous deoxyuridine, led to intracellular accumulation of deoxyuridine triphosphate (dUTP) and incorporation of deoxyuridine monophosphate (dUMP) into DNA. When newly synthesized DNA was extracted from DDMP-treated cells that had been labeled with deoxyuridine for up to 3 min, most of the DNA synthesized was no larger than 4 S on alkaline sucrose gradients. In contrast, the predominant form of newly synthesized alkali-stable DNA in cells not treated with drug was larger than 4 S. Abnormal progression of DNA synthesis, degradation of newly synthesized DNA, or both occurred as a delayed consequence of DDMP treatment in the absence of exogenous deoxyuridine when thymidine was used to label DNA of DDMP-treated stability of antifolate-induced misincorporation of dUMP into DNA was not elucidated, it was clear that antifolates can directly perturb the quality as well as the quantity of DNA synthesized by drug-treated cells.