The stimulation of arachidonic acid metabolism by organic lead and tin compounds in human HL-60 leukemia cells

Abstract

The liberation of fatty acids, above all arachidonic acid, in hyman blood cells is involved in numerous health problems or physiological mechanisms. The activity of cellular phospholipases leads to lipid metabolites such as eicosanoids, platelet activating factor, diacylglycerol, and inositolphosphates that are capable of mediating such pathological symtoms. The results presented here demonstrate that organic heavy metal compounds induce arachidonic acid liberation or its rearrangement within the lipid classes of HL-60 cells before a loss in viability can be detected. Four of the compounds tested, triethyllead (Et 3Pb +), diethyllead (Et 2Pb 2+), trimethyllead (Me 3Pb +), and trimethyltin (Me 3Sn +), show a threshold concentration at which the viability of the cells is drastically decreased after 60 to 180 min incubation, whereas dibutyltin (But 2Sn 2+) induces a constant increase of cell death during the whole incubation time. In the case of threshold concentrations, the compounds stimulate a loss of arachidonic acid within the phospholipids and an increase of free fatty acid and eicosanoids before cell death could be detected. An important fact is the rearrangement of arachidonic acid within the lipid classes of these cells induced by metal concentrations that were not able to kill the cells within the given time. Primarily affected is phosphatidylethanolamine which loses arachidonic acid and, to a minor extent, phosphatidylcholine. Portions of the liberated fatty acid were then metabolized and/or shifted into neutral lipids and other phospholipids. All compounds tested show comparable effects, although at different concentrations. The toxicities of the compounds can be ordered as follows: Et 3Pb + ⩾ Et 2Pb 2+ > But 2Sn 2+ ⩾ Me 3Pb + ≫ Me 3Sn + ⩾ Pb 2+ The cellular shape change following incubation with metal compounds is a further strong indication of a change in the membrane lipids. The cells lose their characteristic microvilli and/or blebs and become round without a loss in viability.