NDLI: Ability of bisbenzylputrescine and propanediamine analogs to modulate the intracellular polyamine pool of P388D1 cells

Content Provider	Springer Nature Link
Author	Badolo, L. Hacq, M. Dubois, J.
Copyright Year	1998
Abstract	The effects of a series of bisbenzyldiamine analogs have been tested on P388D1 cell line in vitro. Their effects on cell growth, polyamine oxidase (PAO) activity and intracellular polyamine content were determined. The cytotoxicity tests were performed in culture medium supplemented with 100 μmol/L aminoguanidine (I), 100 μmol/L aminoguanidine and 100 μmol/L N,N′-bis(2,3-butadienyl)-1,4-butanediamine (MDL 72,527) (II), and finally 100 μmol/L aminoguanidine and 200 μmol/L D,L-difluoromethylornithine (DFMO) (III). The IC50 values under conditions I and III were similar, suggesting that inhibition of ornithine decarboxylase by DFMO did not affect the biological effect of our derivatives. Spermine and spermidine remained nontoxic in conditions I and III. However in the condition II, the toxicity of all tested compounds (excepted spermidine) was increased, suggesting that the inhibition of cellular PAO increased their toxicity.The enzymatic test of PAO showed that at high doses inhibition of this enzyme by putrescine analogs occurred, while the N-methylated propanediamine derivative increased the enzyme activity; however, these results do not correlate with cytotoxicity tests. When these derivatives were incubated for 48 h with the cells, all of them increased the cell content in putrescine (∼160%) and spermine (∼145%) and decreased the spermidine content (∼75%) without any modification of the total amount of polyamine.The correlation between the cytotoxic results and the intracellular polyamine determination shows that the increase in spermine content along with the inhibition of retroconverting PAO enzyme increases the toxic effect of tested compounds (including spermine), suggesting that spermine toxicity is more important in the absence of intracellular oxidation processes.
Starting Page	419
Ending Page	428
Page Count	10
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	14
Issue Number	6
e-ISSN	15736822
Language	English
Publisher	Kluwer Academic Publishers
Publisher Date	1998-01-01
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Pharmacology/Toxicology Veterinary Medicine Animal Anatomy / Morphology / Histology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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