Wantika ChantaraPiyajit WatcharasitApinya ThiantanawatJutamaad SatayavivadMahidol UniversityChulabhorn Research Institute2018-08-202018-08-202006-11-01Journal of Applied Toxicology. Vol.26, No.6 (2006), 517-523109912630260437X2-s2.0-33845271003https://repository.li.mahidol.ac.th/handle/20.500.14594/23250Acrylonitrile (ACN) is classified by IARC as a probable carcinogen. Chronic exposure to ACN increases the incidence of tumors in various organs of test animals, including the brain and lung. ERK1/2 activation plays crucial roles in cell proliferation and is involved in many steps of tumor progression. Therefore, this study examined whether ACN altered the activation state of ERK1/2 in human neuroblastoma SK-N-SH cells. Treatment of these cells with ACN greatly increased phosphorylation of ERK1/2 in dose- and time-dependent manners. This effect was inhibited by PD 98059 and U 0126, specific inhibitors of MEK, indicating that MEK, an upstream activator of ERK1/2, was directly involved in ACN-induced ERK1/2 activation. Furthermore, the activation of ERK1/2 by ACN was attenuated by inhibition of PKC with GF 109203X, rottlerin and prolonged incubation with PMA (phorbol 12-myristate 13-acetate). This demonstrated the participation of PKC in the ACN-stimulated activation of ERK1/2. Taken together, our results indicate that ACN-induced ERK1/2 activation involves PKC through a MEK-dependent pathway. Copyright © 2006 John Wiley & Sons, Ltd.Mahidol UniversityEnvironmental SciencePharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1002/jat.1171