Inhibition of metabolic coupling by metals.
Several metals were evaluated in cell cultures for their ability to inhibit metabolic coupling, the intercellular transfer of low-molecular-weight metabolites by directly connecting gap junctions. To monitor inhibition of metabolic coupling, wild-type Chinese hamster V79 cells proficient in metabolism of 6-thioguanine (6-TG) were cocultured with mutant V79 cells unable to metabolize 6-TG to its toxic metabolite (6-TG-resistant cells). In the presence of 6-TG, inhibition of metabolic coupling by the metals was manifested as increased recovery of 6-TG-resistant cells compared to recovery in untreated cocultures. The toxic metal compounds, arsenic(V) acid, mercury(II) chloride, lead(II) acetate, and nickel(II) chloride, significantly (p less than .05) increased recovery of 6-TG-resistant cells at concentrations that did not alter cell survival. However, because the increased recovery observed with nickel showed no concentration dependence, its importance may be negligible. Cadmium chloride increased 6-TG-resistant cell recovery only at a toxic concentration, and zinc sulfate failed to increase recovery. These data demonstrate that some metal compounds inhibit metabolic coupling, and suggest that inhibition of junctional communication should be further evaluated as a potential mechanism of toxicity of some metals.
Loch-Caruso
R
R
Department of Environmental and Industrial Health, School of Public Health, University of Michigan, Ann Arbor 48109-2029.
Corcos
I A
IA
Trosko
J E
JE
D000818:Animals; D001151:Arsenic / Q000633:toxicity; D002104:Cadmium / Q000633:toxicity; D019256:Cadmium Chloride; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D007365:Intercellular Junctions / Q000187:drug effects*; D008627:Mercuric Chloride / Q000633:toxicity; D008660:Metabolism / Q000187:drug effects*; D008670:Metals / Q000633:toxicity*; D009532:Nickel / Q000633:toxicity; D009942:Organometallic Compounds / Q000633:toxicity; D013431:Sulfates / Q000633:toxicity; D013866:Thioguanine / Q000037:antagonists & inhibitors / Q000378:metabolism; D015032:Zinc / Q000633:toxicity; D019287:Zinc Sulfate
D008670:Metals; D009942:Organometallic Compounds; D013431:Sulfates; D002104:Cadmium; D008627:Mercuric Chloride; C022838:nickel chloride; D019287:Zinc Sulfate; D009532:Nickel; D013866:Thioguanine; D015032:Zinc; D019256:Cadmium Chloride; D001151:Arsenic; C008261:lead acetate