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. 2019 Jan;32(1):27-36.
doi: 10.1293/tox.2018-0015. Epub 2018 Nov 18.

Effects of aflatoxin B1 on the cell cycle distribution of splenocytes in chickens

Hang Li  1   2 , Ke Guan  1   2 , Zhicai Zuo  1   2 , Fengyuan Wang  1   2 , Xi Peng  3 , Jing Fang  1   2 , Hengmin Cui  1   2 , Yi Zhou  4 , Ping Ouyang  2 , Gang Su  2 , Zhengli Chen  2
Affiliations

Effects of aflatoxin B1 on the cell cycle distribution of splenocytes in chickens

Hang Li et al. J Toxicol Pathol. 2019 Jan.

Abstract

The purpose of the present study was to evaluate effects of aflatoxin B1 (AFB1) on the cell cycle and proliferation of splenic cells in chickens. A total of 144 one-day-old Cobb male chickens were randomly divided into 2 equal groups of 72 each and were fed on diets as follows: a control diet and a 0.6 mg/kg AFB1 diet for 21 days. The AFB1 diet reduced body weight, absolute weight and relative weight of the spleen in broilers. Histopathological lesions in AFB1 groups were characterized as slight congestion in red pulp and lymphocytic depletion in white pulp. Compared with the control group, the expression levels of ataxia-telangiectasia mutated (ATM), cyclin E1, cyclin-dependent kinases 6 (CDK6), CDK2, p53, p21 and cyclin B3 mRNA were significantly increased, while the mRNA expression levels of cyclin D1, cdc2 (CDK1), p16, p15 were significantly decreased in the AFB1 groups. Significantly decreased proliferating cell nuclear antigen (PCNA) expression and arrested G0G1 phases of the cell cycle were also seen in the AFB1 groups. In conclusion, dietary AFB1 could induce cell cycle blockage at G0G1 phase and impair the immune function of the spleen. Cyclin D1/CDK6 complex, which inhibits the activin/nodal signaling pathway, might play a significant role in the cell cycle arrest induced by AFB1.

Keywords: AFB1; G0G1phase; cell cycle arrest; chicken; mechanism; spleen.

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Figures

Fig. 1.
Fig. 1.
The effects of dietary AFB1 on body weight and absolute weight and relative weight of the spleen. Notes: Data are presented with the means ± standard deviation (n = 6). *p<0.05 compared with control group, **p<0.01 compared with control group.
Fig. 2.
Fig. 2.
Photomicrographs of hematoxylin and eosin stained chicken spleen. Notes: (A) the control group at 7 days of age; (B) the control group at 14 days of age; (C) the control group at 21 days of age; (D) the AFB1 group at 7 days of age; (E) the AFB1 group at 14 days of age; (F) the AFB1 group at 21 days of age; (Triangles) congestion in the red pulp; (Stars) lymphocytic depletion in white pulp. Bars = 50 μm.
Fig. 3.
Fig. 3.
Cell cycle phase distribution of splenic cell. a: Effect of AFB1 on cell cycle phase distribution of spleen in chicken (%). b: Histogram of splenocyte cell cycle by flow cytometry. Notes: Data are presented with the means ± standard deviation (n = 6). *p<0.05 compared with control group, **p<0.01 compared with control group.
Fig. 4.
Fig. 4.
Immunohistochemistry of the spleen. a: Expression of PCNA protein by immunohistochemistry in the spleen. b: Integrated optical density (IOD sum) of PCNA protein expression in the spleen. Notes: A, B, and C showing the control group at 7, 14, and 21 days respectively; E, F, and H showing the AFB1 group at 7, 14, and 21 days respectively; D and H showing negative control in the control group and the AFB1 group respectively. Bars = 10 μm. Data are presented with the mean ± standard deviation (n = 10). * means p<0.05 compared with the control group, ** means p<0.01 compared with the control group.
Fig. 5.
Fig. 5.
The levels of the ATM, cyclinB3, cyclinD1, CyclinE1, cdc2, CDK6, CDK2, p53, p21, p15, p16, and PCNA mRNA expression in the spleen. Notes: Data are presented with the means ± standard deviation (n = 6). *p<0.05 compared with control group, **p<0.01 compared with control group.
Fig. 6.
Fig. 6.
Schematic diagram of the proposed the molecular mechanism of AFB1 arrest cell cycle in chicken spleen.
See this image and copyright information in PMC

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