| Summary: | 碩士 === 國立臺灣大學 === 毒理學研究所 === 82 === Exposure of NIH3T3 cells with alkylating agent methyl methane-
sulfonate(MMS) leads to the transient induction of c-jun gene.
Several lines of evidence have shown that the activation of
protein kinases can accelerate c-jun mRNA transcription, but
our result clearly demonstrated that pretreatment with
different kinase inhibitors did not alter the MMS-induced c-jun
transcript expression.When both parental NIH3T3 cells and v-Ha-
ras transformed NIH3T3 cells are expose to MMS, we found the
kinetics of c-jun induction of these two cell lines are the
same, but that of DNA damage are quite different. Additionally,
benzamide, a specific inhibitor of poly(ADP-ribosyl)
transferase, potentiates MMS-induced DNA damage level in NIH3T3
cells but has no significant difference on c-jun mRNA
accumulation when comparing with the degree of MMS treated
alone. When MMS treatment followed depletion of intracellular
GSH by BSO, the induction of c-jun mRNA was inhibited severely.
Furthermore, the degree of c-jun induction correlates with the
level of intracellular GSH. Finally we suggest the primary
message comes from the disturbance of GSH pool. Methylating
modification on Cys residue of GSH may be an important
intermediate triggering signals to elevating the transcription
of c-jun gene.
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