Effects of di(2-ethylhexyl)phthalate exposure on 1,2-dimethyhydrazine-induced colon tumor promotion in rats

Hsin-Pao Chen; Min-Hsiung Pan; Yuan-Yi Chou; Chieh Sung; Kuo-Hsin Lee; Chung-Man Leung; Ping-Chi Hsu

doi:10.1016/j.fct.2017.03.014

Effects of di(2-ethylhexyl)phthalate exposure on 1,2-dimethyhydrazine-induced colon tumor promotion in rats

Food Chem Toxicol. 2017 May:103:157-167. doi: 10.1016/j.fct.2017.03.014. Epub 2017 Mar 8.

Authors

Hsin-Pao Chen¹, Min-Hsiung Pan², Yuan-Yi Chou³, Chieh Sung³, Kuo-Hsin Lee⁴, Chung-Man Leung³, Ping-Chi Hsu⁵

Affiliations

¹ 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.
² Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
³ Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung 811, Taiwan.
⁴ Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung 824, Taiwan.
⁵ Department of Safety, Health and Environmental Engineering, National Kaohsiung First University of Science and Technology, Kaohsiung 811, Taiwan. Electronic address: pchsu@nkfust.edu.tw.

PMID: 28284729
DOI: 10.1016/j.fct.2017.03.014

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.

Keywords: Colorectal cancer; Cyclin D1; Cyclooygenase-2; Di(2-ethylhexyl)phthalate; Vascular endothelial growth factor; β-Catenin.

MeSH terms

1,2-Dimethylhydrazine / toxicity*
Animals
Colonic Neoplasms / chemically induced*
Colonic Neoplasms / metabolism
Colonic Neoplasms / pathology*
Cyclin D1 / metabolism
Cyclooxygenase 2 / metabolism
Diethylhexyl Phthalate / toxicity*
Liver / drug effects
Male
Organ Size / drug effects
Rats, Sprague-Dawley
Vascular Endothelial Growth Factor A / metabolism
beta Catenin / metabolism

Substances

Ccnd1 protein, rat
Ctnnb1 protein, rat
Vascular Endothelial Growth Factor A
beta Catenin
vascular endothelial growth factor A, rat
Cyclin D1
Diethylhexyl Phthalate
Cyclooxygenase 2
Ptgs2 protein, rat
1,2-Dimethylhydrazine