Intracellular conversions of deoxyribonucleosides by Novikoff rat hepatoma cells and effects of hydroxyurea

Intracellular conversions of deoxyribonucleosides by Novikoff rat hepatoma cells and effects of hydroxyurea
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Novikoff大鼠肝癌细胞内脱氧核糖核苷的转化及羟基脲的影响

DOI:
10.1002/jcp.1040830302
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发表时间:
1974
影响因子:
5.6
通讯作者:
J. Erbe
J. Erbe
中科院分区:
生物学2区
文献类型:
--
作者:
P. Plagemann;J. Erbe

文献摘要

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通过培养的Novikoff大鼠肝癌细胞,3H标记的脱氧腺苷和脱氧鸟苷进入核酸的比例约为80%进入RNA, 20%进入DNA。在全细胞和无细胞提取物的研究中阐明了其结合途径。脱氧腺苷很快被脱去为脱氧肌苷。整个细胞形成的脱氧肌苷大部分被运输出细胞并在培养基中积累。脱氧肌苷和脱氧鸟苷的一部分分别被嘌呤核苷磷酸化酶磷酸化为次黄嘌呤和鸟嘌呤。后者随后通过次黄嘌呤-鸟嘌呤磷酸核糖基转移酶分别转化为IMP和GMP。嘌呤脱氧核糖核苷主要通过这一途径进入DNA,随后核糖核苷还原酶还原ADP和GDP,尽管细胞摄取的脱氧腺苷和脱氧鸟苷中有一小部分似乎分别被直接磷酸化为dAMP和dGMP。脱氧鸟苷只与RNA和DNA的鸟嘌呤残基结合。脱氧腺苷也主要结合到RNA和DNA的鸟嘌呤残基中,尽管酸溶池中脱氧腺苷的放射性几乎完全与ATP相关。在标记脱氧肌苷、肌苷或次黄嘌呤时观察到类似的标记模式。另一方面,嘧啶脱氧核糖核苷是DNA中各自碱基的特定前体。
The incorporation of 3H‐labeled deoxyadenosine and deoxyguanosine into nucleic acids by cultured Novikoff rat hepatoma cells is about 80% into RNA and 20% into DNA. The pathways of incorporation have been elucidated in studies with whole cells and cell‐free extracts. Deoxyadenosine is very rapidly deaminated to deoxyinosine. Most of the deoxyinosine formed by whole cells is transported out of the cells and accumulates in the medium. A portion of the deoxyinosine, and deoxyguanosine are phosphorolyzed by purine nucleoside phosphorylase to hypoxanthine and guanine, respectively. The latter are subsequently converted by hypoxanthine‐guanine phosphoribosyl transferase to IMP and GMP, respectively. Incorporation of the purine deoxyribonucleosides into DNA is mainly via this pathway and the subsequent reduction of ADP and GDP by ribonucleoside reductase, although a small proportion of the deoxyadenosine and deoxyguanosine taken up by the cells seems to be directly phosphorylated to dAMP and dGMP, respectively. Deoxyguanosine is incorporated only into guanine residues of RNA and DNA. Deoxyadenosine is also mainly incorporated into guanine residues of RNA and DNA, although the radioactivity of deoxyadenosine in the acid‐soluble pool is almost exclusively associated with ATP. A similar labeling pattern is observed with labeled deoxyinosine, inosine or hypoxanthine. The pyrimidine deoxyribonucleosides, on the other hand, are specific precursors for their respective bases in DNA.