Effect of low level zinc pretreatment on zinc-mediated toxicity in different lung cell lines.
Reduced toxicity of high zinc exposure was observed after pretreatment of various lung cells with nonlethal zinc concentrations. This effect became significant when various parameters of cytotoxicity were assessed (e.g., inhibition of protein synthesis, depletion of reduced glutathione [GSH], increase of oxidized glutathione [GSSG], release of lactate dehydrogenase [LDH]). Similar protective effects by zinc have already been shown by several investigators for a variety of toxicity studies dealing with cadmium, in vitro and in vivo. Zinc-induced toxicity has been linked to glutathione metabolism and cellular GSH contents. Activity of glutathione reductase (GR) and rates of glutathione synthesis were identified as determinants of zinc (cyto)toxicity. However, these variables were virtually unaffected in our adapted cells. Consequently, another variable appears to be crucial for modulating cellular suscepticibility in zinc pretreated cells. Protection in our cells was achieved by pretreatment with 80-120 micromol/L zinc chloride for 24-72 h, roughly 10-fold more zinc in the medium than is normally found in human plasma. Protection was not observed when the cells were concomitantly exposed to cycloheximide, an inhibitor of protein synthesis, or actinomycin D, an inhibitor of RNA synthesis, but it was found in the presence of amanitin, an inhibitor of mRNA synthesis. It is therefore concluded that the altered zinc tolerance of pretreated cells is not attributable to the induction of metallothionein.
Walther Straub-Institut für Pharmakologie und Toxikologie der Ludwig-Maximilians Universität München, Germany.
U I
UI
Walther
H
H
Mückter
B
B
Wallner
U
U
Bergen
S
S
Duggen
G
G
Unsinn
S C
SC
Walther
B
B
Fichtl
D002460:Cell Line; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015032:Zinc / Q000008:administration & dosage* / Q000633:toxicity*
D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D007770:L-Lactate Dehydrogenase; D005980:Glutathione Reductase; D005978:Glutathione; D015032:Zinc