Induction of the c-jun protooncogene expression by areca nut extract and arecoline on oral mucosal fibroblasts.
To investigate the mechanisms of areca quid (AQ)-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in human oral mucosal fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found that treatment of cells with 200 microg/ml ANE or 10 microg/ml arecoline for 1 h induced about three-fold increase in c-jun mRNA levels. This increase was transient and the level of c-jun mRNAs returned rapidly to control levels thereafter. However, ANE and arecoline did not induce c-fos mRNA expression at detectable levels. During AQ chewing, oral mucosal cells are continuously stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene by ANE and arecoline may be one of the mechanisms in the carcinogenesis of oral squamous cell carcinoma in Taiwan. Furthermore, we observed that pre-incubation of cells with either N-acetyl-cysteine [a glutathione (GSH) precursor] or L-buthionine-S,R-sulfoximine (a specific inhibitor of GSH biosynthesis) had a minimal effect on arecoline-induced c-jun expression. Therefore, arecoline-induced c-jun expression is independent of GSH depletion.
Ho
T J
TJ
School of Dentistry, College of Medicine, National Taiwan University, 1 Chang-Te Street, 100, Taipei, Taiwan.
Chiang
C P
CP
Hong
C Y
CY
Kok
S H
SH
Kuo
Y S
YS
Yen-Ping Kuo
M
M
D001114:Areca / Q000009:adverse effects*; D001115:Arecoline / Q000009:adverse effects*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000453:epidemiology / Q000235:genetics; D009152:Mutagenicity Tests; D010946:Plants, Medicinal; D016755:Proto-Oncogene Proteins c-jun / Q000187:drug effects*; D013624:Taiwan / Q000453:epidemiology / Q000208:ethnology
D016755:Proto-Oncogene Proteins c-jun; D001115:Arecoline