Effect of 1,3,6-triaminohexane and 1,4,7-triaminoheptane on growth and polyamine metabolism in SV-3T3 cells treated with 2-difluoromethylornithine.
The possibility that one or both of the synthetic triamines, 1,3,6-triaminohexane and 1,4,7-triaminoheptane, could substitute for the naturally occurring polyamines in the growth of SV-3T3 cells was investigated. It was found that these triamines did lead to a restoration of growth in cells in which spermidine content had been depleted by exposure to the ornithine decarboxylase inhibitor 2-difluoromethylornithine. This resumption of a normal growth rate occurred prior to the reduction in the content of cellular decarboxylated S-adenosylmethionine, suggesting that this nucleoside (which increases in concentration several hundred-fold in cells treated with 2-difluoromethylornithine) does not cause the reduction of cell growth. However, unlike the increase in cell growth brought about by spermidine, which continued indefinitely, the increase produced by 1,3,6-triaminohexane or 1,4,7-triaminoheptane was transient. Cell growth in the presence of 2-difluoromethylornithine and these triamines stopped after about three or four population doublings. This corresponded to the time at which the intracellular spermine content of the cells was reduced to values less than 20% of normal. It is suggested that the increased growth rate of spermidine-depleted cells in response to these triamines is due to their uptake into the cell and ability to displace spermine from intracellular sites, thus making spermine available to fulfill the polyamine function(s) essential for growth. These results indicate that the naturally occurring polyamines spermidine or spermine are essential for continued cell growth and cannot be replaced by analogues containing only primary amino groups.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002472:Cell Transformation, Viral; D000518:Eflornithine; D005347:Fibroblasts / Q000378:metabolism* / Q000502:physiology; D006536:Heptanes / Q000494:pharmacology*; D006586:Hexanes / Q000494:pharmacology*; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D011073:Polyamines / Q000378:metabolism* / Q000494:pharmacology*; D011700:Putrescine / Q000378:metabolism / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000031:analogs & derivatives / Q000378:metabolism; D013539:Simian virus 40; D013095:Spermidine / Q000378:metabolism / Q000494:pharmacology
D006536:Heptanes; D006586:Hexanes; D011073:Polyamines; C048363:1,4,7-triaminoheptane; C012702:S-adenosyl-3-methylthiopropylamine; C048364:1,3,6-triaminohexane; D012436:S-Adenosylmethionine; D009952:Ornithine; D013095:Spermidine; D011700:Putrescine; D000518:Eflornithine