Epidermal Growth Factor Mediates Di-N-Octyl Phthalate-Induced Hepatocyte Proliferation

Abstract

Certain chemicals used in manufacturing plastics are linked to severe, negative health effects such as cancer. Di-N-Octylphthalate (DNOP) is a phthalate found in many plastics and has been linked with hepatocellular carcinoma. The aim of this research project was to study the effect of DNOP on the proliferation of normal mouse hepatocytes and the growth factor implicated. The expression of several growth factors and receptors (epidermal growth factor receptor (egfr), epidermal growth factor (egf), insulin-like growth factor 1 receptor (igf1r), insulin-like growth factor 1 (igf1), insulin-like growth factor 2 (igf2), and hepatocyte growth factor (hgf)) was assessed in normal hepatocytes AML-12 cell line by RT-PCR and qPCR. The rate of cell proliferation of AML-12 cells was measured using MTT cell proliferation assay kit. DNOP at 0.1% caused an increase in expression of egf at 24h, 48h, and 72 h. This result was confirmed by Western blot. DNOP did not cause changes in any of other studied genes. The rate of cell proliferation increased in those cells treated with 0.1% DNOP at 72 h and 96 h. In conclusion, our observation indicates that DNOP, through an increase in the expression of egf, acts as a proliferative agent in normal mouse hepatocytes. Funding Source: Center for Undergraduate Research and Scholarship, Department of Biological Sciences and Scholarly Activity Award