Effects of di(2-ethylhexyl)phthalate exposure on 1,2-dimethyhydrazine-induced colon tumor promotion in rats
Journal
Food and Chemical Toxicology
Journal Volume
103
Pages
157-167
Date Issued
2017
Author(s)
Abstract
Di(2-ethylhexyl)phthalate (DEHP) may cause carcinogenicity in the liver; however, few have detailed on the potential effects of DEHP exposure on colorectal cancer. Male Sprague-Dawley rats received i.p. injections of 1,2-dimethylhydrazine (DMH) once-a-week for the first 4 weeks, and rats in each group were treated with DEHP through oral gavage daily for either 7, 10 or 15 weeks; after which, all rats were euthanized and their colons were assessed (a) morphologically for aberrant crypt foci (ACF) or tumors, (b) cytologically for mitotic index (MI), and (c) immunohistochemically for the expression of β-catenin, cyclooygenase (COX)-2, vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), cyclin D1, and c-myc. Our results indicated that the mean total ACF, tumor incidence, and MI were significantly higher in the DEHP-treated DMH compared to control and the DEHP-alone groups. The level of β-catenin and cyclin D1 was increased in DEHP-exposed rats. Expression of β-catenin, COX-2, VEGF, and cyclin D1 was significantly higher in the combined DMH and DEHP-treated rats by comparison to that of the DMH group. In conclusion, this study indicates that exposure to DEHP may exacerbate DMH-induced colon tumorigenesis and provides impetus to evaluate the effect of DEHP in conjunction with other carcinogens. ? 2017 Elsevier Ltd
Subjects
Colorectal cancer; Cyclin D1; Cyclooygenase-2; Di(2-ethylhexyl)phthalate; Vascular endothelial growth factor; β-Catenin
SDGs
Other Subjects
1,2 dimethylhydrazine; beta catenin; cyclin D1; cycline; cyclooxygenase 2; Myc protein; phthalic acid bis(2 ethylhexyl) ester; vasculotropin; 1,2 dimethylhydrazine; beta catenin; Ccnd1 protein, rat; Ctnnb1 protein, rat; cyclin D1; cyclooxygenase 2; phthalic acid bis(2 ethylhexyl) ester; Ptgs2 protein, rat; vascular endothelial growth factor A, rat; vasculotropin A; aberrant crypt focus; animal experiment; animal model; animal tissue; Article; colon carcinogenesis; colon tumor; controlled study; male; mitosis index; nonhuman; protein expression; rat; tumor promotion; animal; chemically induced; colon tumor; drug effects; liver; metabolism; organ size; pathology; Sprague Dawley rat; 1,2-Dimethylhydrazine; Animals; beta Catenin; Colonic Neoplasms; Cyclin D1; Cyclooxygenase 2; Diethylhexyl Phthalate; Liver; Male; Organ Size; Rats, Sprague-Dawley; Vascular Endothelial Growth Factor A
Type
journal article