Section for Experimental Biomedicine, Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Norway.
Section for Experimental Biomedicine, Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Norway.
Chemosphere. 2019 Jan;214:534-542. doi: 10.1016/j.chemosphere.2018.09.126. Epub 2018 Sep 24.
A multitude of cancer types, including breast, testicular, liver and colorectal cancer, have associations with exposure to Persistent Organic Pollutants (POPs). The present study aimed to investigate whether a mixture of POPs could affect intestinal tumorigenesis in the A/J Min/+ mouse, a model for human colorectal cancer (CRC). Pollutants were selected for their presence in Scandinavian food products and the mixture was designed based on defined human estimated daily intake levels. Mice were exposed through the diet, at control, low and high mixture concentrations, for 10 weeks. In a separate experiment, mice also received one subcutaneous injection of Azoxymethane (AOM) to explore whether this carcinogenic compound influenced the effect of the POPs. Intestinal tumorigenesis was examined by surface microscopy and histopathology. Moderate and dose-dependent increases in tumorigenesis were observed after dietary POP exposure. The AOM treatment alone stimulated the growth of colonic lesions, but did not increase the formation of new lesions. Combined AOM treatment and POP exposure demonstrated a synergistic effect on lesion formation in the colon, and to a lesser extent in the small intestine. This synergy was also evident by an increased number of malignant colonic tumors (carcinomas). In conclusion, the study shows that a mixture of POPs interacted synergistically with a known carcinogen (AOM), causing increased intestinal tumorigenesis in the A/J Min/+ mouse model.
许多癌症类型,包括乳腺癌、睾丸癌、肝癌和结直肠癌,都与接触持久性有机污染物(POPs)有关。本研究旨在探讨 POPs 混合物是否会影响 A/J Min/+ 小鼠的肠道肿瘤发生,A/J Min/+ 小鼠是人类结直肠癌(CRC)的模型。选择这些污染物是因为它们存在于斯堪的纳维亚的食品中,并且根据人类估计的每日摄入量设计了混合物。通过饮食,将污染物以对照、低和高混合物浓度的方式暴露于小鼠,持续 10 周。在一个单独的实验中,小鼠还接受了一次皮下注射氧化偶氮甲烷(AOM),以探讨这种致癌化合物是否会影响 POPs 的作用。通过表面显微镜和组织病理学检查来检查肠道肿瘤发生情况。在接受饮食 POP 暴露后,观察到肿瘤发生呈中度和剂量依赖性增加。AOM 单独处理刺激了结肠病变的生长,但并未增加新病变的形成。AOM 处理和 POP 暴露的联合作用对结肠病变的形成表现出协同作用,在小肠中则作用较小。在结肠癌(癌)中恶性肿瘤数量的增加也表明了这种协同作用。总之,该研究表明,POPs 混合物与已知致癌剂(AOM)相互作用,协同作用导致 A/J Min/+ 小鼠模型中肠道肿瘤发生增加。