Action Mechanism of 2-(2-Hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic Acid-with Special Reference to Selective Inhibition of DNA Synthesis in Ascites Hepatoma AH 13 Cells in Culture

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概要

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• The mode of action of 2-(2-hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid (HQ II) was studied using mainly ascites hepatoma AH 13 (AH 13) cells in culture. 1) In vitro, HQ II causes hemolysis of rabbit erythrocytes and injures cancer cells. However, these effects are not appeared in the medium containing some amounts of serum. 2) Even in the culture containing serum, HQ II inhibits the proliferation of AH 13 cells and causes selective inhibition of desoxyribonucleic acid (DNA) synthesis. These actions are mostly restored by washing or addition of Fe salts. 3) Uptake of ^3H-thymidine, ^3H-deoxycytidine (^3H-CdR), and ^3H-cytidine (^3H-CR) to the cellular acid-solubles are not decreased by HQ II treatment. However, the incorporations to DNA in turn are prominently inhibited. 4) The conversion of ^3H-CR to ^3H-CdR nucleotides is inhibited in the cells treated with HQ II. 5) The exogenous addition of a certain composition of deoxyribonucleosides to the medium can suppress the inhibitory effect of HQ II on DNA synthesis. 6) The reduction of ^<14>C-CR diphosphate to ^<14>C-CdR nucleotides in cell-free extracts of AH 13 cells is prominently inhibited by the agent. HQ II causes the cell membrane injury and/or inhibits selectively DNA synthesis in AH 13 cells. The results suggest that the inhibition of DNA synthesis caused by HQ II having metal-chelate-forming ability may be due to the interaction of the agent with the extracellular and/or intracellular Fe (in which ribonucleotide reductase may be involved.).

• 公益社団法人日本薬学会の論文
• 1975-01-25

著者

• 越村 三郎

  Department of Serology, Kanazawa Medical University

• 越村 三郎

  Kanazawa Medical University

• 氏家 俊光

  Department of Chemistry, Research Institute of Tuberculosis, Kanazawa University

• 氏家 俊光

  Department Of Experimental Therapeuticus Cancer Research Institute Kanuzawa University

• 越村 三郎

  Department Of Serology Kanazawa Medical University

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• Action Mechanism of 2-(2-Hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic Acid-with Special Reference to Selective Inhibition of DNA Synthesis in Ascites Hepatoma AH 13 Cells in Culture
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