Cadmium inhibits EGF-induced DNA synthesis but increases cellular glutathione levels in NRK-49F cells.
The effects of cadmium (CdCl2) on epidermal growth factor (EGF) induced DNA synthesis and on cellular glutathione (GSH) content in growth-arrested NRK-49F cells were studied. The cadmium effects were compared with those of L-buthionine-(S,R)-sulfoximine (BSO). EGF at a concentration of 10 ng/ml was found to stimulate DNA synthesis (as judged by [3H]thymidine incorporation) in growth-arrested NRK-49F cells. CdCl2 inhibited this EGF-induced DNA synthesis in a dose-dependent fashion. It also increased significantly cellular GSH content in both growth arrested and EGF-stimulated NRK-49F cells. This effect of CdCl2 was contrary to that of BSO, which depleted cellular GSH. Although BSO both inhibited EGF-induced DNA synthesis and decreased cellular GSH content in EGF-stimulated NRK-49F cells, these two BSO effects showed dissimilar dose dependencies. BSO and CdCl2 together inhibited EGF-induced DNA synthesis in NRK-49F cells in an additive fashion. These results demonstrate that cadmium inhibition of EGF-induced DNA synthesis in NRK-49F cells is not due to an effect on cellular GSH content. Both cadmium and BSO inhibit EGF-induced DNA synthesis in NRK-49F cells, but probably through different mechanisms. Although GSH may be involved in regulation of DNA synthesis, BSO-induced inhibition of EGF-stimulated DNA synthesis in NRK-49F cells does not in its dose-dependency correlate with GSH depletion.
Kang
Y J
YJ
Department of Zoology and Genetics, Iowa State University, Ames 50011.
Enger
M D
MD
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D002104:Cadmium / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000963:Antimetabolites; D002104:Cadmium; D014316:Tritium; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004815:Epidermal Growth Factor; D004247:DNA; D005978:Glutathione; D013936:Thymidine