The risk of developing colorectal cancer (CRC) could be associated with red and processed meat intake. Experimental data supports that hemin iron, found abundantly in red meat, promotes CRC in mice and rats, while indole-3 carbinol (I3C) and synbiotics (syn) exert anti-carcinogenic activities in most studies of colon carcinogenesis. This study aimed to investigate the modifying effects of I3C and syn (inulin + Bifidobacterium lactis), given separately or together, on dimethylhidrazine (DMH)-induced colon carcinogenesis in hemin-fed rats. All animals were given four subcutaneous DMH injections and then, two weeks after carcinogen exposure, they began a basal diet containing hemin, hemin + I3C, hemin + syn, or hemin + I3C + syn for 23 weeks. The combination of I3C + syn significantly increased fecal water genotoxicity, tumor volume and invasiveness when compared to the hemin-fed control group. The groups fed I3C or syn alone had a significant reduction in the number of preneoplastic aberrant crypt foci (ACF) lesions compared to the hemin-fed group. Dietary I3C also reduced fecal water genotoxicity. Gene expression analysis of colorectal tumors demonstrated that the combination of dietary I3C + syn increased transcript levels for Raf1 and decreased tumor progression and invasiveness related to the genes Cdh1 and Appl1. This analysis also revealed that the Tnf and Cdh1 genes were significantly up- and down-regulated, respectively, in tumors of rats that received I3C, in comparison with the hemin-fed group. These findings reveal that the joint administration of I3C and syn enhanced the development of colon tumors induced by DMH in hemin-fed rats, while they potentially reduced ACF development when given alone.

患结直肠癌（CRC）的风险可能与红色和加工肉的摄入量有关。实验数据支持在红肉中大量发现的血红素铁可促进小鼠和大鼠的CRC，而在大多数结肠癌的研究中，吲哚3甲醇（I3C）和合生元（syn）发挥抗癌活性。这项研究旨在研究I3C和syn（菊粉+乳双歧杆菌）的修饰作用 ）分别给予或给予一起，以二甲基hi嗪（DMH）诱导的血红素喂养的大鼠结肠癌发生。对所有动物进行四次皮下DMH注射，然后，在致癌物暴露后两周，开始基础饮食，其中包含hemin，hemin + I3C，hemin + syn或hemin + I3C + syn。与喂食血红素的对照组相比，I3C + syn的组合显着增加了粪便水的遗传毒性，肿瘤体积和侵袭性。单独喂食I3C或syn的组与喂食血红素的组相比，肿瘤前异常隐窝灶（ACF）病变的数量显着减少。饮食中的I3C还可以减少粪便水的遗传毒性。大肠肿瘤的基因表达分析表明，饮食I3C + syn的组合增加了Raf1和Rf1的转录水平。降低了与基因Cdh1和Appl1相关的肿瘤进展和侵袭性。这项分析还表明，与接受血红素喂养的组相比，接受I3C的大鼠肿瘤中的Tnf和Cdh1基因分别显着上调和下调。这些发现表明，I3C和syn的联合给药增强了在喂食血红素的大鼠中DMH诱导的结肠肿瘤的发展，而当单独给予时，它们可能会降低ACF的发展。