Acceleration of benzo(a)pyrene-induced colon carcinogenesis by Western diet in a rat model of colon cancer

IF 2.9 Q2 TOXICOLOGY
Kelly L. Harris , Kenneth J. Harris , Leah D. Banks , Samuel E. Adunyah, Aramandla Ramesh
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Abstract

Colorectal cancer (CRC) is the third leading cause of cancer-related mortalities in the USA and around 52,550 people were expected to die from this disease by December 2023. The objective of this study was to investigate the effect of diet type on benzo(a)pyrene [B(a)P]-induced colon cancer in an adult male rat model, the Polyposis In the Rat Colon (PIRC) kindred type. Groups of PIRC rats (n = 10) were fed with AIN-76A regular diet (RD) or Western diet (WD) and received 25, 50 and 100 µg B(a)P/kg body wt. via oral gavage for 60 days. Rats fed diets alone, but no B(a)P, served as controls. After exposure, rats were euthanized; colon and liver samples were analyzed for activation of drug metabolizing enzymes (DMEs) CYP1A1, CYP1B1, SULT and GST. Plasma and tissue samples were analyzed by reverse phase-HPLC for B(a)P metabolites. In addition to these studies, DNA isolated from colon and liver tissues was analyzed for B(a)P-induced DNA adducts by the 32P-postlabeling method using a thin-layer chromatography system. Western diet consumption resulted in a marked increase in DME expression and B(a)P metabolite concentrations in rats that were administered 100 µg/kg B(a)P + WD (p < 0.05) compared to other treatment groups. Our findings demonstrate that WD accelerates the development of colon tumors induced by B(a)P through enhanced biotransformation, and the products of this process (metabolites) were found to bind with DNA and form B(a)P-DNA adducts, which may have given rise to colon polyps characterized by gain in tumor number, sizes, and dysplasia.

Abstract Image

在大鼠结肠癌模型中,西方饮食加速苯并(a)芘诱导的结肠癌发生
结肠直肠癌(CRC)是美国癌症相关死亡的第三大原因,预计到 2023 年 12 月将有约 52550 人死于这种疾病。本研究的目的是调查饮食类型对苯并芘[B(a)P]诱发成年雄性大鼠结肠癌的影响。用 AIN-76A 普通饮食(RD)或西式饮食(WD)喂养各组 PIRC 大鼠(n = 10),并通过口服灌胃法每公斤体重分别摄入 25、50 和 100 µg B(a)P,连续喂养 60 天。大鼠作为对照组,只喂食不含 B(a)P 的食物。暴露后,对大鼠实施安乐死;分析结肠和肝脏样本,以检测药物代谢酶(DMEs)CYP1A1、CYP1B1、SULT 和 GST 的活化情况。血浆和组织样本通过反相高效液相色谱法分析 B(a)P 代谢物。除这些研究外,还利用薄层色谱系统,采用 32P 后标记法分析了从结肠和肝脏组织中分离出的 DNA,以检测 B(a)P 诱导的 DNA 加合物。与其他治疗组相比,摄入西式饮食会导致 100 µg/kg B(a)P + WD 大鼠的 DME 表达和 B(a)P 代谢物浓度显著增加(p < 0.05)。我们的研究结果表明,WD 通过增强生物转化加速了 B(a)P 诱导的结肠肿瘤的发展,并且发现这一过程的产物(代谢物)与 DNA 结合并形成 B(a)P-DNA 加合物,这可能导致结肠息肉,其特征是肿瘤数量、大小和发育不良的增加。
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来源期刊
Current Research in Toxicology
Current Research in Toxicology Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
4.70
自引率
3.00%
发文量
33
审稿时长
82 days
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