Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction.

Sequential dietary exposure to aflatoxin B1 and fumonisin B1 in F344 rats increases liver preneoplastic changes indicative of a synergistic interaction.
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DOI:
10.1016/j.fct.2016.07.017
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发表时间:
2016-09
影响因子:
4.3
通讯作者:
Wang, Jia-Sheng
Wang, Jia-Sheng
中科院分区:
农林科学2区
文献类型:
--
作者:
Qian, Guoqing;Tang, Lili;Lin, Shuhan;Xue, Kathy S.;Mitchell, Nicole J.;Su, Jianjia;Gelderblom, Wentzel C.;Riley, Ronald T.;Phillips, Timothy D.;Wang, Jia-Sheng

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黄曲霉毒素B1(AFB 1)和伏马菌素B1(FB 1)的膳食联合暴露及其在肝细胞癌发生中的相互作用是毒理学和公共卫生领域特别关注的问题。在这项研究中,我们评估了在F344大鼠致癌模型中,单次和连续膳食暴露于黄曲霉毒素B1和FB 1的肝脏癌前效应。血清生化改变、肝脏组织病理学改变和肝脏谷胱甘肽S转移酶阳性(GST-P+)病灶的形成是检查的主要结局参数。与仅AFB 1处理相比,仅FB 1处理诱导较少的异型增生,以及更多的凋亡和有丝分裂。与单独使用真菌毒素治疗相比,AFB 1和FB 1连续治疗导致肝细胞发育异常、凋亡和病灶改变的数量增加。更重要的是,与AFB 1或FB 1单独给药组相比,AFB 1和FB 1顺序给药协同增加了肝脏GTP-P+病灶的数量约7.3倍和12.9倍,并分别增加了GST-P+病灶的平均大小6倍和7.5倍。此外,与单次给药组相比,序贯给药后肝脏ALT和AST水平显著升高。结果表明,饲料中的黄曲霉毒素B1和FB 1在诱导肝脏GST-P+灶形成的相互作用,并提供信息模型未来的干预研究。
Dietary co-exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) and their interaction on hepatocellular carcinogenesis is of particular concern in toxicology and public health. In this study we evaluated the liver preneoplastic effects of single and sequential dietary exposure to AFB1 and FB1 in the F344 rat carcinogenesis model. Serum biochemical alterations, liver histopathological changes, and the formation of liver glutathione S transferase positive (GST-P+) foci were the major outcome parameters examined. Compared to the AFB1-only treatment, the FB1-only treatment induced less dysplasia, and more apoptosis and mitoses. Sequential AFB1 and FB1 treatment lead to increased numbers of dysplasia, apoptosis and foci of altered hepatocytes, as compared to either mycotoxin treatment alone. More importantly, sequential exposure to AFB1 and FB1 synergistically increased the numbers of liver GTP-P+ foci by approximately 7.3-and 12.9-fold and increased the mean sizes of GST-P+ foci by 6- and 7.5-fold, respectively, as compared to AFB1- or FB1-only treatment groups. In addition, liver ALT and AST levels were significantly increased after sequential treatment as compared to single treatment groups. The results demonstrate the interactive effect of dietary AFB1 and FB1 in inducing liver GST-P+ foci formation and provide information to model future intervention studies.
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