This study investigates the effects of fenthion and terbufos, two organophosphorous pesticides, on DNA damage, tumor-related gene expression, and apoptosis in HepG2 cells. We found that exposure to concentrations ranging from 50 to 200 mu M of fenthion and terbufos for 2 hr caused significant death in HepG2 cells. Both compounds induced DNA damage in a concentration-dependent manner as measured using the alkaline comet assay. Tumor-related genes (jun, myc, and fos) and apoptosis-related genes (socs3, tnfaip3, ppp1r15a, and nr4a1) were up-regulated by both compounds. Finally, both compounds induced apoptosis. The results demonstrate that both terbufos and fenthion induce DNA damage and should be considered potentially hazardous to humans. Environ. Mol. Mutagen. 52:529-537, 2011. (C) 2011 Wiley-Liss, Inc.