Mechanisms of spermine toxicity in baby-hamster kidney (BHK) cells. The role of amine oxidases and oxidative stress.
Spermine was toxic to BHK-21/C13 cells in the absence of any extracellular metabolism of the amine. Inhibition of copper-containing amine oxidases with aminoguanidine partially prevented the response, whereas inhibition of polyamine oxidase with MDL-72,527 exacerbated the effect. Oxidation by an intracellular copper-containing amine oxidase may be involved in the toxicity of spermine, whereas the polyamine-interconversion pathway appears to play a cytoprotective role. There was no evidence for spermine imposing a state of oxidative stress within the cells. Inhibition of catalase and glutathione reductase did not alter the cytotoxicity of spermine, and there was no excretion of oxidized glutathione into the extracellular medium. The results suggest that spermine itself can exert a toxic effect directly on the cells.
Brunton
V G
VG
Department of Medicine, University of Aberdeen, Scotland, U.K.
Grant
M H
MH
Wallace
H M
HM
D000818:Animals; D002330:Carmustine / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D005980:Glutathione Reductase / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D007668:Kidney; D007700:Kinetics; D008954:Models, Biological; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology*; D000097667:Polyamine Oxidase
D002330:Carmustine; D002374:Catalase; D005980:Glutathione Reductase; D006146:Guanidines; D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D011700:Putrescine; D013096:Spermine; D000097667:Polyamine Oxidase; C044445:MDL 72527; C004479:pimagedine