Arecoline cytotoxicity on human oral mucosal fibroblasts related to cellular thiol and esterase activities

Betel quid (BQ) chewing is associated with an increased risk of oral submuc ous fibrosis (OSF) and oral cancer in India and many south-east Asian count ries. Recently, we have shown that arecoline is cytotoxic to cultured human oral mucosal fibroblasts. This study investigated protective effects of va rious agents against the cytotoxicity of arecoline and its mechanisms. Arec oline, at concentrations of 0.2 and 0.4 mM, decreased the cell numbers by 3 8% and 63%, respectively. At a concentration of 2 mM, N-acetyl-L-cysteine [ a glutathione (GSH) synthesis precursor] could prevent arecoline-induced cy totoxicity. The decrease in cell numbers was reduced to 17% relative to con trol. Extracellular addition of esterase at a concentration of 0.1 U/ml cou ld almost completely protect the oral mucosal fibroblast (OMF) from arecoli ne-induced cytotoxicity. Arecoline is a muscarinic receptor agonist. Howeve r, atropine, a muscarinic receptor antagonist was unable to protect the cel ls from arecoline cytotoxicity at a concentration of 10 mu M. Pretreatment of OMF with 50 mu M buthionine sulfoximine (a cellular GSH synthesis inhibi tor) or 0.5 mM diethylmaleate (a cellular GSH depleting agent) potentiated the cytotoxic effects of arecoline. These results indicate that cytotoxicit y of arecoline on OMF is associated with cellular GSH levels and esterase a ctivities. Factors that induce the GSH synthesis or esterase activity of or al mucosal cells can be used for future chemoprevention of BQ chewing-relat ed lesions. (C) 1999 Elsevier, Science Ltd. All rights reserved.