The nephrotoxin dichlorovinylcysteine induces expression of the protooncogenes c-fos and c-myc in LLC-PK1 cells--a comparative investigation with growth factors and 12-O-tetradecanoylphorbolacetate.
Previous studies in kidney cells showed that S-(1,2-dichlorovinyl)-L-cysteine (DCVC) induces both direct DNA damage and DNA double-strand breaks by activation of Ca(2+)-dependent endonucleases. The objective of this study was to investigate the effects of DCVC on the expression of the protooncogenes c-fos and c-myc in cultured kidney cells (LLC-PK1). Supplementation of the incubation medium with 10% FCS after 24 hr incubation in 0.2% FCS resulted in a clear, but comparatively weak induction of the expression of c-fos and c-myc in LLC-PK1 cells. Addition of 500 microns DCVC to the high serum incubation medium induced a further three-fold increase of the transcript levels. A similar increase in the absolute amount of c-fos mRNA was induced by a mixture of growth factors (epidermal growth factor/insulin/transferrin) and of c-myc mRNA with 12-O-tetradecanoylphorbolacetate. However, the kinetics of gene expression were different. In the presence of DCVC the expression of c-fos and c-myc increased continuously in a time-dependent manner during the entire incubation period. In contrast, with growth factors and 12-O-tetradecanoyl-phorbolacetate the maximum transcript levels were detected after 0.5 hr (c-fos) and 1 hr (c-myc), respectively; thereafter, a slight decrease was observed up to the end of the incubation time.
Vamvakas
S
S
Institut für Toxikologie, Universität Würzburg. Federal Republic of Germany.
Köster
U
U
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000633:toxicity; D004249:DNA Damage; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos; D016259:Genes, myc; D006133:Growth Substances / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D012313:RNA / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006133:Growth Substances; C039961:S-(1,2-dichlorovinyl)cysteine; D012313:RNA; D003545:Cysteine; D013755:Tetradecanoylphorbol Acetate