THE NEPHROTOXIN DICHLOROVINYLCYSTEINE INDUCES EXPRESSION OF THE PROTOONCOGENES C-FOS AND C-MYC IN LLC-PK(1) CELLS - A COMPARATIVE INVESTIGATION WITH GROWTH-FACTORS AND 12-O-TETRADECANOYLPHORBOLACETATE
S. Vamvakas et U. Koster, THE NEPHROTOXIN DICHLOROVINYLCYSTEINE INDUCES EXPRESSION OF THE PROTOONCOGENES C-FOS AND C-MYC IN LLC-PK(1) CELLS - A COMPARATIVE INVESTIGATION WITH GROWTH-FACTORS AND 12-O-TETRADECANOYLPHORBOLACETATE, Cell biology and toxicology, 9(1), 1993, pp. 1-13
Previous studies in kidney cells showed that S-(1,2-dichlorovinyl)-L-c
ysteine (DCVC) induces both direct DNA damage and DNA double-strand br
eaks by activation of Ca2+-dependent endonucleases. The objective of t
his 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 inc
ubation in 0.2% FCS resulted in a clear, but comparatively weak induct
ion of the expression of c-fos and c-myc in LLC-PK1 cells. Addition of
500 mum DCVC to the high serum incubation medium induced a further th
ree-fold increase of the transcript levels. A similar increase in the
absolute amount of c-fos mRNA was induced by a mixture of growth facto
rs (epidermal growth factor/insulin/transferrin) and of c-myc mRNA wit
h 12-O-tetradecanoylphorbolacetate. However, the kinetics of gene expr
ession were different. In the presence of DCVC the expression of c-fos
and c-myc increased continuously in a time-dependent manner during th
e entire incubation period. In contrast, with growth factors and 12-O-
tetradecanoyl-phorbolacelate the maximum transcript levels were detect
ed 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.