Chronic Consumption of DNOP Induces an Epithelial-to-mesenchymal Transition State in Mouse Liver

Abstract

Hepatocellular carcinoma is the cancer of the liver cells that is developed over time by the evolution of pre-neoplastic lesions. Di-n-octylphthalate (DNOP) is a plasticizer used to keep plastics flexible. If mice are exposed to DNOP, it causes an increase in pre-neoplastic hepatic lesions. Previously, our group found that DNOP increased the expression of transforming growth factor β (tgf-β) in AML-12 cells. Because tgf-β induces an epithelial-to-mesenchymal transition (EMT) state in mouse hepatocyte in vitro, our goal was to study the extent to which DNOP induces an EMT state in mouse liver. Two antibodies were used: anti-albumin antibody (a hepatocyte marker), and anti-vimentin (a mesenchymal cell maker). We first treated AML-12 cells with 0.1 % DNOP for 24, 48 and 72 h. No changes in the expression of albumin was seen. Because the limited time of 72 h may not have allowed sufficient time for a change in the phenotype, mice were fed diet containing 0.1 % DNOP for a month. We found that DNOP decreased the levels of albumin, whereas increased the levels of vimentin. In conclusion, chronic consumption of DNOP induces an EMT state in mouse liver. This mechanism may be involved in formation of hepatic pre-neoplastic lesions.