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Reduction of adenine nucleotide content of clone 4 mdck cells: Effects on multiplication, protein synthesis, and morphology
Author(s) -
Ladino C.,
Schneeberger E. E.,
Rabito C. A.,
Lynch R. D.
Publication year - 1989
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041400122
Subject(s) - nucleotide , theophylline , adenosine , biology , biochemistry , protein biosynthesis , enzyme , clone (java method) , microbiology and biotechnology , adenosine monophosphate , dna synthesis , trypsin , incubation , dna , endocrinology , gene
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 which 3 H‐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.