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The nephrotoxin dichlorovinylcysteine induces expression of the protooncogenesC-fos andC-myc in LLC-PK1 cells—A comparative investigation with growth factors and 12-O-tetradecanoylphorbolacetate

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Abstract

Previous studies in kldney cells showed that S-(l,2-dichloroviny1)-L-cysteitle (DCVC) induces both direct DNA damage and DNA double-strand breaks by activation of Ca2+-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 pm DCVC to the high serum incubation medium induced a further three-jold 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 factorlinsulini transferrin) and of c-myc mRNA with 12-0-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 incubatiorl period. In contrast, with growth factors and 12-0-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 incubakion lime.

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Abbreviations

dCTP:

deoxycytidinetriphosphate

DCVC:

S-(1,2-dichlorovinyl)-L-cysteine

DMEM:

Dulbecco's modified Eagle medium

EGF:

epidermal growth factor

EIT:

epidermal growth factor/insulin/transferrin

FCS:

fetal calf serum

LDH:

lactate dehydrogenase

PBS:

phosphate buffered saline

SDS:

sodiumdodecylsulfate

TPA:

12-O-tetradecanoylphorbolacetate

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  1. Institut für Toxikologie, Universität Würzburg, Versbacher Str. 9, D-8700, Würzburg, Germany

    S. Vamvakas & U. Köster

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  1. S. Vamvakas
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Vamvakas, S., Köster, U. The nephrotoxin dichlorovinylcysteine induces expression of the protooncogenesC-fos andC-myc in LLC-PK1 cells—A comparative investigation with growth factors and 12-O-tetradecanoylphorbolacetate. Cell Biol Toxicol 9, 1–13 (1993). https://doi.org/10.1007/BF00755136

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