Hydrogen peroxide promotes transformation of rat liver non-neoplastic epithelial cells through activation of epidermal growth factor receptor

Previous studies demonstrated that hydrogen peroxide (H2O2) is a tumor promoter in the rat liver epithelial cell line T51B. We investigated the pathway linking H2O2 to tumor promotion. H2O2 can directly induce tyrosine phosphorylation of epidermal growth factor receptor (EGFR). H2O2 and epidermal growth factor exerted similar effects on the induction of early growth response genes, disruption of gap junction communication, triggering of calcium inflow, and promotion of transformation. Furthermore, the effect of H2O2 on tumor promotion was blocked by abrogation of EGFR activation. Our results suggested that tumor promotion by H2O2 is mediated mainly through activation of EGFR in T51B cells. (C) 2001 Wiley-Liss, Inc.