Abstract
Aflatoxin B1 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 G0G1 phase and G2M phase arrest of cell cycle in the bursa of Fabricius in broilers exposed to dietary AFB1. 144 one-day-old healthy Cobb broilers were randomly divided into two groups and fed on control diet and 0.6 mg·Kg−1 AFB1 diet for 3 weeks. Histological observation showed that AFB1 induced the increase of nuclear debris and vacuoles in lymphoid follicle of BF. Results of flow cytometry studies showed that bursal cells arrested in G2M phase at 7 days of age and blocked in G0G1 phase at 14 and 21 days of age following exposure to AFB1. The qRT-PCR analysis indicated that cell cycle arrested in G2M phase via ATM-Chk2-cdc25-cyclin B/cdc2 pathway, and blocked in G0G1 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 AFB1 diet induced G2M and G0G1 phase blockage of BF cells in different periods, and different pathways were activated in different arrested cell cycle phase.
Highlights
Aflatoxin B1 (AFB1), secondary metabolites generated by the fungi Aspergillus flavus and Aspergillus parasiticus, usually can contaminate agricultural products and threaten food safety[1]
Many studies showed that AFB1 induce cell cycle arrest at different phases depending on the cell types, such as the accumulation of G2M phase cell in thymocytes[26] and broiler’s jejunal epithelia[13], the increase of S-phase cell population in human bronchial epithelial cells[14], and the arrest at G0G1 phases in lymphocytes[16] and liver cells[27]
The present study showed that consumption of 0.6 mg·kg−1 AFB1 diet induced the arrest at G2M phase in bursal cells of broilers at 7 days of age and the blockage at G0G1 phases at 14 and 21 days of age
Summary
Aflatoxin B1 (AFB1), secondary metabolites generated by the fungi Aspergillus flavus and Aspergillus parasiticus, usually can contaminate agricultural products and threaten food safety[1]. Previous studies have shown that AFB1 could induce G2M phase arrest in broiler’s jejunum in vivo[12,13]; S-phase accumulation in human bronchial epithelial cell in vitro[14]; G0G1 phase blockage in hepatocytes of rat in vivo[15]. AFB1-induced S-phase arrest might be mediated via inhibiting Wnt/β-catenin signaling route in HepG2 cells in vitro[17], it may be triggered by activating ATM/ATR, Chk[2], and p53 signaling pathways in human bronchial epithelial cells[14]. A broiler model was used to clarify the signaling pathway related molecular mechanisms involved in the cell cycle arrest of BF cells after dietary AFB1 treatement. We analyzed the histological lesions of BF, cell cycle phase distribution of bursal cells, mRNA expression levels of regulatory molecules involved in G0G1, S and G2M transitions, and the protein expression level of proliferating cell nuclear antigen (PCNA)
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