Effects of a heterogeneous set of xenobiotics on growth and plasma membranes of mammalian and fungal cell cultures.
A comparison of the toxicity of 45 selected, heterogenous substances on two test organisms of different taxonomic levels, the yeast Saccharomyces cerevisiae and Chinese hamster ovary (CHO) cells, was made. In addition, effects on the yeast plasma membrane-integrated H(+)-ATPase and on the CHO adenosine uptake system were investigated. For all test systems, log EC50 values highly correlated with log EC20 values. Good correlations were obtained between CHO proliferation rate and yeast growth rate (r = 0.80). However, CHO cells were about four times more sensitive than yeast. A good accordance was also found between effects on yeast cell growth and on the H(+)-ATPase, indicating a plasma membrane impairment as a major cause of cytotoxicity. These findings were supported by correlations of log EC20 values with the log Pow as a measure for lipophilicity. Although the test systems demonstrated different dependencies, the main trend reflected an increasing toxicity with increasing lipophilicity. Comparisons with data from in vivo test systems suggest that these in vitro test systems could be implemented for initial estimation of basic toxicity and the detection of outliers thereby reducing the number of tests with higher animals.
Cascorbi
I
I
Free University of Berlin, Institute of Biochemistry and Molecular Biology, Germany.
Bittrich
H
H
Ricklinkat
J
J
Voss
W
W
Seyfarth
A
A
Forêt
M
M
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D006180:Proton-Translocating ATPases / Q000187:drug effects / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development*; D013045:Species Specificity; D015262:Xenobiotics / Q000633:toxicity*
D015262:Xenobiotics; D006180:Proton-Translocating ATPases; D000241:Adenosine