Inhibitors for the mutagenicities of colon carcinogens, 1,2-dimethylhydrazine and azoxymethane, in the host-mediated assay.

Inhibitory effects of several chemicals on the mutagenicities of 1,2-dimethylhydrazine (DMH) and azoxymethane (AOM) for Salmonella typhimurium G46 in the host-mediated assay were investigated. They were carbon disulfide (CS2), tetraethylthiuram disulfide (disulfiram, DSF), sodium diethyldithiocarbamate (SDDC), ethylene-bis(dithiocarbamato) manganese (Maneb), pyrazole (PZ), aminoacetonitrile hydrogen sulfate (AAN), and sodium selenite (SE). All the compounds, except for SE, inhibited the mutagenicities of DMH and AOM.     

TiaochangXiaoliu decoction inhibits azomethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer by regulating immune response

BackgroundTiaochangXiaoliu decoction (TXD) has an anti-tumor effect in clinical practice. We further investigated the role of TXD in colorectal cancer (CRC).MethodsMouse models of CRC were induced by azomethane (AOM)/dextran sulfate sodium (DSS), with sixty male C57BL/6 mice randomly divided into six groups (10 mice/group): a control group, AOM/DSS group, TXD at low dose (L-dose) group, middle dose (M-dose) group, high dose (H-dose) group, and Celecoxib (Cel) group. The colorectum, serum, and plasma of mice in each group was collected following sacrifice to record the number of tumors. HE staining was utilized for observing pathological damage to colorectal tissues, ELISA used for detecting INF-γ, IL-2, and TNF-α expression in serum, and flow cytometry used for measuring the proportion of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cells in plasma.ResultsCompared with the control group, the AOM/DSS group showed tumor masses in the colorectum and different degrees of pathological damage in the intestine. AOM/DSS induction also resulted in an increase in INF-γ, IL-2, and TNF-α expression in serum, and a decrease in the percentages of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cells(P<0.05). In comparison with the AOM/DSS group, with the increase of TXD dose, the number of tumors decreased significantly, and intestinal structure and mucosal inflammatory cell infiltration also improved. Further, in comparison with the AOM/DSS group, all three doses of TXD and celecoxib caused an increase in the contents of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cells in plasma. In addition, in the M-dose, H-dose, and Cel groups, INF-γ, IL-2, and TNF-α expression showed a marked decrease, and the reduction in these two groups treated with TXD was dose-dependent.ConclusionsTXD leads to a marked reduction in the number of tumors and inflammatory cell infiltration in CRC mice. This decoction significantly decreased the levels of INF-γ, IL-2, and TNF-α in serum, and increased the contents of CD4⁺, CD8⁺, CD4⁺/CD8⁺, and NK cell in the plasma of mice with AOM/DSS-induced CRC.     

湿热-痰结-瘀毒型小鼠肠癌模型的建立

目的建立一种湿热-痰结-瘀毒的大肠癌动物模型,为中医药预防大肠癌实验的多方位多角度开展提供模型保障。方法将60只雄性小鼠随机分为实验A组、B组及C组,每组20只。A组腹腔注射氧化偶氮甲烷(Azoxymethane,AOM)12.5 mg/kg;B组腹腔注射AOM 10 mg/kg;C组一直为空白组,腹腔注射等量生理盐水,均1次。随后A、B两组行3个循环周期,自由饮用2.5%葡聚糖硫酸钠5 d+自由饮用无菌用水16 d为1个循环周期;C组自由饮用无菌用水,3组均采用高脂颗粒饲料喂养。造模结束后,断颈处死小鼠观察其瘤体组织变化。结果与C组比较,A组和B组的造模前后的体质量差异有统计学意义(P<0.05),B组体质量变化大于A组(P<0.05);A组腺癌成癌率较高,B组腺瘤成瘤率较高,差异均有统计学意义(P<0.05);造模过程中A组死亡率大于C组,差异有统计学意义(P<0.05)。组织病理学显示A组腺癌细胞排列紊乱,乳头内间质少;B组腺瘤细胞排列呈大小不一的管状结构,腺上皮细胞数目增多,核细长,呈不同程度的异型性。结论AOM 10 mg/kg剂量组适合腺瘤(痰结)模型,AOM 12.5 mg/kg更适合恶性肿瘤(瘀毒)模型。