Key Laboratory of Animal Diseases and Environmental Hazards of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China.
College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan, 611130, PR China.
Sci Rep. 2018 Jan 29;8(1):1770. doi: 10.1038/s41598-018-20164-z.
Aflatoxin B shows potent hepatotoxic, carcinogenic, genotoxic, immunotoxic potential in humans and many species of animals. The aim of this study was to clarify the underlying mechanism of GG phase and GM phase arrest of cell cycle in the bursa of Fabricius in broilers exposed to dietary AFB. 144 one-day-old healthy Cobb broilers were randomly divided into two groups and fed on control diet and 0.6 mg·Kg AFB diet for 3 weeks. Histological observation showed that AFB induced the increase of nuclear debris and vacuoles in lymphoid follicle of BF. Results of flow cytometry studies showed that bursal cells arrested in GM phase at 7 days of age and blocked in GG phase at 14 and 21 days of age following exposure to AFB. The qRT-PCR analysis indicated that cell cycle arrested in GM phase via ATM-Chk2-cdc25-cyclin B/cdc2 pathway, and blocked in GG phase through ATM-Chk2-cdc25-cyclin D/CDK6 pathway and ATM-Chk2-p21-cyclin D/CDK6 route. In a word, our results provided new insights that AFB diet induced GM and GG phase blockage of BF cells in different periods, and different pathways were activated in different arrested cell cycle phase.
黄曲霉毒素 B 对人类和许多动物物种具有很强的肝毒性、致癌性、遗传毒性和免疫毒性。本研究旨在阐明日粮中添加黄曲霉毒素 B 对肉鸡法氏囊细胞周期 G1 期和 G2/M 期阻滞的作用机制。将 144 只 1 日龄健康科宝肉鸡随机分为两组,分别饲喂基础日粮和含 0.6 mg·kg-1 黄曲霉毒素 B 的日粮 3 周。组织学观察结果表明,黄曲霉毒素 B 诱导法氏囊淋巴滤泡核碎片和空泡增加。流式细胞术研究结果表明,暴露于黄曲霉毒素 B 后,法氏囊细胞在 7 日龄时被阻滞在 G2/M 期,在 14 日龄和 21 日龄时被阻滞在 G1 期。qRT-PCR 分析表明,细胞周期通过 ATM-Chk2-cdc25-cyclin B/cdc2 途径被阻滞在 G2/M 期,通过 ATM-Chk2-cdc25-cyclin D/CDK6 途径和 ATM-Chk2-p21-cyclin D/CDK6 途径被阻滞在 G1 期。总之,我们的研究结果提供了新的见解,即黄曲霉毒素 B 日粮在不同时期诱导法氏囊细胞 G1 期和 G2/M 期阻滞,不同的途径在不同的阻滞细胞周期中被激活。