The interaction of ethanol and exogenous arachidonic acid in the formation of leukotrienes and prostaglandin D2 in mastocytoma cells

The present studies were undertaken to examine the hypothesis that ethanol could effect cellular biosynthesis in the murine mastocytoma cell of prostaglandins and leukotrienes, oxidative metabolites of arachidonic acid, at concentrations that could be encountered $\text{in vivo}$ as well as during $\text{in vitro}$ experiments. The effects of ethanol which encompass these concentration ranges (200–1000 mg%) can be summarized as follows: first in the absence of exogenous arachidonic acid, ethanol caused a dose dependent decrease in the production of leukotrienes which was statistically significant at 200 mg%. At 1000 mg%, ethanol caused a 20–50% decrease in leukotrienes and a 21% decrease in the amount of prostaglandins D₂ (PGD₂) formed in these cells. Secondly, when cells were incubated with exogenous arachidonic acid (14 μg/ml), large increases in both PGD₂ and leukotrienes occurred. Under these conditions, ethanol caused a further increase in the amount of leukotrienes and a small increase in the amount of PGD₂ formed. This stimulatory effect was specific for ethanol since neither t-butanol nor n-butanol caused the enhanced production of leukotrienes with exogenous arachidonic acid. Thus, these experiments sugsests that ethanol affects metabolsim of arachidonic acid at reasonably low doses (200–400 mg%) of ethanol in a manner dependent on the free arachidonic acid in the tissue. Also, $\text{in vitro}$ experiments in which ethanol is used as a solvent for arachidonic acid could be greatly affected by high levels of ethanol (500–1000 mg%) which are frequently utilized.