Allylamine toxicity in embryonic myocardial myocyte reaggregate cultures.
This study investigated the response of chick myocardial myocyte reaggregates (MMR) to allylamine, which is specifically toxic to the cardiovascular system, and its putative toxic metabolite, acrolein. Toxicity was assessed by determining cellular ATP content, spontaneous beating and ultrastructural alterations. Both allylamine and acrolein caused a dose-dependent loss of beating and depletion of cellular ATP content. Treatment with either 10 or 100 mum-allylamine produced marked alterations in reaggregate tissue morphology at all times, which was characterized by widespread myocyte necrosis and a reduction in tissue compactness. Exposure of aggregates to acrolein produced generalized tissue destruction following administration of either 10 or 100 mum-acrolein. The concentration of allylamine required to cause loss of MMR beating was greatly increased when incubations were carried out in serum-free medium. It is suggested that the presence of benzylamine oxidase in serum contributes to the toxicity of allylamine to MMR, by metabolizing allylamine to acrolein. This proposal is supported by the finding that the related amines n-methylallylamine and diallylamine had no effect on spontaneous beating, which may be because they are very poor substrates for benzylamine oxidase. The data presented demonstrate that allylamine is highly toxic to MMR, and we believe that further investigations into the role of serum in allylamine toxicity would improve our understanding of the biochemical basis of its action.
Kesingland
K
K
D.H. Department of Toxicology, St Bartholomew's Hospital Medical College, University of London, Dominion House, 59 Bartholomew Close, London EC1 7ED, UK.
Earl
L K
LK
Roberts
J C
JC
Jones
H B
HB