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, ex pression of c-fos and c-jun protooncogenes was examined in human oral mucos al fibroblasts after exposure to areca nut extracts (ANE) or arecoline. We found that treatment of cells with 200 mu g/ml ANE or 10 mu g/ml arecoline for 1 h induced about three-fold increase in c-jun mRNA levels. This increa se was transient and the level of c-jun mRNAs returned rapidly to control l evels thereafter. However, ANE and arecoline did not induce c-fos mRNA expr ession at detectable levels. During AQ chewing, oral mucosal cells are cont inuously stimulated by ANE and arecoline. Persistent induction of the c-jun protooncogene by ANE and arecoline may be one of the mechanisms in the car cinogenesis of oral squamous cell carcinoma in Taiwan. Furthermore, we obse rved that pre-incubation of cells with either N-acetyl-cysteine [a glutathi one (GSH) precursor] or L-buthionine-S,R-sulfoximine (a specific inhibitor of GSI-l biosynthesis) had a minimal effect on arecoline-induced c-jun expr ession. Therefore, arecoline-induced c-jun expression is independent of GSH depletion. (C) 2000 Elsevier Science Ltd. All rights reserved.