1-Aminooxy-3-aminopropane reversibly prevents the proliferation of cultured baby hamster kidney cells by interfering with polyamine synthesis.
The effects on cultured baby hamster kidney cells of 1-aminooxy-3-aminopropane, a potent new inhibitor of mammalian ornithine and S-adenosylmethionine decarboxylases and of spermidine synthase, were studied. At 0.5 mM concentration in the culture medium, the drug did not interfere with the transmethylation-transsulfuration pathway nor with the polyamine transport system, but it blocked the proliferation and macromolecule synthesis of the cells and reduced the cellular spermidine level to less than 10% of the control value at identical cell density. These changes were accompanied by a total cessation of the excretion of putrescine, spermidine, and acetylated polyamines into the culture medium, greatly increased activity of ornithine and S-adenosylmethionine decarboxylases, and an accumulation of both decarboxylated and intact S-adenosylmethionine. These effects were reversed by the removal of the inhibitor from the culture medium or by supplementing the medium with either 0.5 mM putrescine or 0.1 mM spermidine. In the former case, however, a lag period of 24 h was necessary for the cells to recover. The elevated concentration of decarboxylated S-adenosylmethionine normalized very slowly but apparently had no harmful effects on the cells. The clonigenic potential of the cells was only slightly reduced by prolonged treatment with 0.5 mM 1-aminooxy-3-aminopropane. Thus, the new drug is not toxic to the cells, but either directly or indirectly stops their proliferation by preventing the adequate formation of putrescine and spermidine.
Hyvönen
T
T
Department of Biochemistry, University of Kuopio, Finland.
Alakuijala
L
L
Andersson
L
L
Khomutov
A R
AR
Khomutov
R M
RM
Eloranta
T O
TO
D000123:Acetyltransferases / Q000378:metabolism; D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D007668:Kidney / Q000166:cytology*; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011073:Polyamines / Q000096:biosynthesis*; D011437:Propylamines / Q000494:pharmacology*; D011700:Putrescine / Q000096:biosynthesis; D013095:Spermidine / Q000096:biosynthesis; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D012437:Adenosylmethionine Decarboxylase; D009955:Ornithine Decarboxylase; D011073:Polyamines; D011437:Propylamines; D011700:Putrescine; D013095:Spermidine; D000099228:Diamine N-Acetyltransferase; C046252:1-aminooxy-3-aminopropane