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

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.