Introduction
The c-fos gene belongs to the family of growth- and differentiation-related
immediate early genes whose expression, in vivo and in vitro, represents the first
measurable response to a variety of chemical and physical stimuli including
tumor promoters and DNA-damaging agents. The expression of c-fos has been
identified as a signal for cell proliferation, but also for apoptosis.
Key Findings:
2R1 mainstream smoke-bubbled phosphate-buffered saline (PBs) induces
c-fos expression in quiescent 3T3 fibroblast cells ...
concentration-dependently. A threshold concentration of approx. 0.015
puffs/ml was observed.
by interfering with transcriptional and posttranscriptional regulatory
components since a slight induction of the c-fos promoter and a strong
stabilization of c-fos transcripts were observed. The translation of smoke-
bubbled PBS-induced c-fos mRNA into protein was confirmed using immuno-
detection methods.
independently of the presence of hydroxyl radicals formed by the Fenton
reactionsince neither o-phenanthroline-anefficient,membranepermeable
scavenger of iron cations - nor catalase were able to reduce cigarette smoke-
dependent c-fos expression at concentrations that were shown to inhibit DNA
strandbreakformation.
the kinetics being different from those reported for physiological inducers
(growth factors, serum), TPA, or stress treatment (heat shock, UV, hydroxyl
radicals).
in a manner very similar to that described for okadaic acid, a specific inhibitor
of cell cycle-specific phosphatases 1 and 2A (PP-1/2A). Cellular effects
shared by smoke-bubbledPBS and okadaic acid invitro are:
kinetics of c-fos expression,
pattern of c-fos expression, i.e., the slight activation of the c-fos
promoter aswell as the stabilization of c-fos mRNA,
partial inhibition of protein synthesis,
induction of stress response genes such as heme oxygenase,
induction of cell cycle arrest, and
inhibition of PP-1/2A enzymatic activities.
associated with a concentration-dependent loss of total cellular glutathione
(GSHtat).
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