title: Effects of di(2-ethylhexyl)phthalate exposure on 1,2-dimethyhydrazine-induced colon tumor promotion in rats.
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.
authors.affiliation: Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung 811, Taiwan; Division of Colon and Rectal Surgery, Department of Surgery, E-DA Hospital, I-Shou University, Kaohsiung 824, Taiwan.
authors.forename: Hsin-Pao
authors.initials: HP
authors.lastname: Chen
authors.affiliation: Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
authors.forename: Min-Hsiung
authors.initials: MH
authors.lastname: Pan
authors.affiliation: Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung 811, Taiwan.
authors.forename: Yuan-Yi
authors.initials: YY
authors.lastname: Chou
authors.affiliation: Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung 811, Taiwan.
authors.forename: Chieh
authors.initials: C
authors.lastname: Sung
authors.affiliation: Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.
authors.forename: Kuo-Hsin
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung 811, Taiwan.
authors.forename: Chung-Man
authors.initials: CM
authors.lastname: Leung
authors.affiliation: Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung 811, Taiwan. Electronic address: pchsu@nkfust.edu.tw.
authors.forename: Ping-Chi
authors.initials: PC
authors.lastname: Hsu
mesh_terms: D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D008099:Liver / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C530106:Ccnd1 protein, rat; C495268:Ctnnb1 protein, rat; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; C467498:vascular endothelial growth factor A, rat; D019938:Cyclin D1; D004051:Diethylhexyl Phthalate; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D019813:1,2-Dimethylhydrazine
keywords: Colorectal cancer; Cyclin D1; Cyclooygenase-2; Di(2-ethylhexyl)phthalate; Vascular endothelial growth factor; β-Catenin