The influence of different growth conditions on the phospholipid composition and on two membrane functions, the Mg-ATPase and the purine transport system, was investigated. Addition of cholinechloride to the growth medium led to a certain rise in the amount of phosphatidylcholine, whereas supplementation with ethanolamine resulted in a considerably higher portion of phosphatidylethanolamine. When yeast cells were cultured at lower temperatures we found more short-chain fatty acids with a higher content of monounsaturated chains as compared to higher growth temperatures. Addition of paraquat, a herbicide which enhances lipid peroxidation by free radicals, reduced the amount of unsaturated fatty acids without influencing their chain length. The altered membrane composition had no influence on the basic mechanism of interaction between ATPase, MgATP, and free Mg2+ ions. However, several kinetic constants such as Km, Vmax, Ka, and especially Ki were influenced to some extent. Whereas the affinity of the purine transport system to its substrate was not significantly changed by the growth conditions, an effect on Vmax could be seen. Lower growth temperatures clearly led to higher maximal uptake velocities. The presence of paraquat during growth resulted in a considerable decrease of Vmax.
The uptake kinetics, accumulation, and metabolism of several radioactively labeled environmental chemicals by the eucaryotic microorganism yeast were studied. The results have shown that this test system rapidly provides information about the extent of uptake and accumulation of such chemicals as a function of various external conditions. Thus, different forms of environmental hazard can be simulated.
In addition, in several cases a correlation between inhibition of functional membrane proteins (adenosine triphosphatase and transport systems) and reduction of the cell growth rate was observed, which suggests that the toxicity of an environmental chemical may often be caused by the result of an interaction with important membrane components. The agreement of these results with acute toxicity data from the literature indicate that yeast is suitable for detecting potential hazards to higher organisms from chemicals.
The first 13 substances of the MEIC (multicentre evaluation study of in vitro cytotoxicity) project were tested in a test system in which the generation time of yeast cells in their logarithmic growth phase was used as the endpoint. Toxic effects, expressed as EC10, EC20 or EC50 values, were correlated with octanol/water partition coefficients. The correlation was found to be very high, indicating that the lipophilicity of substances is a key parameter for describing the toxicity of chemicals.
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