Department of Toxicogenomics, GROW institute of Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
Laboratorio de Carcinogénesis y Toxicología, Unidad de Biomedicina, FES-Iztacala, UNAM, Estado de México, Mexico.
Sci Rep. 2018 Jun 27;8(1):9738. doi: 10.1038/s41598-018-28063-z.
Titanium dioxide as a food additive (E171) has been demonstrated to facilitate growth of chemically induced colorectal tumours in vivo and induce transcriptomic changes suggestive of an immune system impairment and cancer development. The present study aimed to investigate the molecular mechanisms behind the tumour stimulatory effects of E171 in combination with azoxymethane (AOM)/dextran sodium sulphate (DSS) and compare these results to a recent study performed under the same conditions with E171 only. BALB/c mice underwent exposure to 5 mg/kg/day of E171 by gavage for 2, 7, 14, and 21 days. Whole genome mRNA microarray analyses on the distal colon were performed. The results show that E171 induced a downregulation of genes involved in the innate and adaptive immune system, suggesting impairment of this system. In addition, over time, signalling genes involved in colorectal cancer and other types of cancers were modulated. In relation to cancer development, effects potentially associated with oxidative stress were observed through modulation of genes related to antioxidant production. E171 affected genes involved in biotransformation of xenobiotics which can form reactive intermediates resulting in toxicological effects. These transcriptomics data reflect the early biological responses induced by E171 which precede tumour formation in an AOM/DSS mouse model.
二氧化钛作为一种食品添加剂（E171）已被证明可促进体内化学诱导的结直肠肿瘤的生长，并诱导转录组变化，提示免疫系统受损和癌症发展。本研究旨在探讨 E171 与氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）联合作用下刺激肿瘤的分子机制，并将这些结果与在相同条件下仅用 E171 进行的最近一项研究进行比较。BALB/c 小鼠通过灌胃接受每天 5mg/kg 的 E171，持续 2、7、14 和 21 天。对远端结肠进行全基因组 mRNA 微阵列分析。结果表明，E171 下调了参与固有和适应性免疫系统的基因，提示该系统受损。此外，随着时间的推移，参与结直肠癌和其他类型癌症的信号基因也发生了调节。关于癌症的发展，通过与抗氧化剂产生相关的基因的调节，观察到与氧化应激相关的潜在作用。E171 影响了参与外源生物转化的基因，这些基因可以形成反应中间体，导致毒理学效应。这些转录组学数据反映了 E171 在 AOM/DSS 小鼠模型中诱导肿瘤形成之前引起的早期生物学反应。
