Reduction of adenine nucleotide content of clone 4 MDCK cells: effects on multiplication, protein synthesis, and morphology.
Reduction of adenine nucleotide content of clone 4 MDCK cells: effects on multiplication, protein synthesis, and morphology.
复制标题
克隆 4 MDCK 细胞腺嘌呤核苷酸含量的减少:对增殖、蛋白质合成和形态的影响。
DOI:
10.1002/jcp.1041400122
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发表时间:
1989
影响因子:
5.6
通讯作者:
Lynch,RD
中科院分区:
文献类型:
--
作者:
Ladino,C;Schneeberger,EE;Rabito,CA;Lynch,RD
The antitumor agent hadacidin (N‐formyl‐hydroxyamino‐acetic acid), at 4 mM, inhibited the multiplication of clone 4 Madin Darby canine kidney (MDCK) cells within 24 hr. Growth resumed rapidly upon replacement of hadacidin with aspartate, an observation consistent with the drug's action as a competitive inhibitor of adenylosuccinate synthetase, an enzyme in adenine nucleotide biosynthesis. Data indicate that the drug‐treated cells were arrested in S phase of the cell cycle. Accompanying inhibition of multiplication was a 16‐fold increase in the area occupied by the cells and a refractoriness to release by treatment with trypsin. None of these changes occurred when 0.5 mM adenosine was included in the incubation mixture containing the inhibitor. Hadacidin decreased the adenosine triphosphate (ATP) and cyclic adenosine monophosphate (cAMP) content of the cells as well as the rate at which3H‐leucine was incorporated into protein. In the presence of 1 mM dibutyryl cAMP and theophylline, the drug had no effect on cell division and protein synthesis. The data suggest that, in clone 4 MDCK cells, the effects of hadacidin are mediated by diminishing the level of cAMP.