Chen Hsin-Pao, Pan Min-Hsiung, Chou Yuan-Yi, Sung Chieh, Lee Kuo-Hsin, Leung Chung-Man, Hsu Ping-Chi
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.
Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
Food Chem Toxicol. 2017 May;103:157-167. doi: 10.1016/j.fct.2017.03.014. Epub 2017 Mar 8.
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.
邻苯二甲酸二（2-乙基己基）酯（DEHP）可能会导致肝脏致癌；然而，很少有人详细研究过DEHP暴露对结直肠癌的潜在影响。雄性Sprague-Dawley大鼠在最初4周每周腹腔注射一次1,2-二甲基肼（DMH），每组大鼠每天通过灌胃给予DEHP，持续7、10或15周；之后，将所有大鼠安乐死，并对其结肠进行评估：（a）形态学上评估异常隐窝病灶（ACF）或肿瘤；（b）细胞学上评估有丝分裂指数（MI）；（c）免疫组织化学评估β-连环蛋白、环氧化酶（COX）-2、血管内皮生长因子（VEGF）、增殖细胞核抗原（PCNA）、细胞周期蛋白D1和c-myc的表达。我们的结果表明，与对照组和单独使用DEHP的组相比，DEHP处理的DMH组的平均总ACF、肿瘤发生率和MI显著更高。DEHP暴露大鼠的β-连环蛋白和细胞周期蛋白D1水平升高。与DMH组相比，联合DMH和DEHP处理的大鼠中β-连环蛋白、COX-2、VEGF和细胞周期蛋白D1的表达显著更高。总之，本研究表明，暴露于DEHP可能会加剧DMH诱导的结肠肿瘤发生，并为评估DEHP与其他致癌物联合作用的效果提供了动力。
