Cell-cycle blockage associated with increased apoptotic cells in the thymus of chickens fed on diets high in fluorine

Three hundred 1-day-old Avian broilers were divided into four groups and fed on control diet (fluorine 23 mg/kg) and high-fluorine (F) diets (400 mg/kg, high-F group I; 800 mg/kg, high-F group II; 1200 mg/kg, high-F group III) for 42 days (n = 75/group). The growth index (GI) was obviously decreased in the three high-F groups, which indicated the inhibited development of thymus. Histopathologically, the population of thymocytes was decreased in the thymic lobule in the three high-F groups. As measured by flow cytometry, thymocytes in G₀/G ₁ phase were significantly increased while thymocytes in S phase, G ₂ + M phase and proliferating index (PI) value were obviously decreased in the three high-F groups. Also, the percentage of apoptotic thymocytes was greatly increased in the three high-F groups when compared with that of control group. At the same time, the occurrence frequencies of apoptotic thymocyte were markedly increased in the three high-F groups, with the appearance of dilated endoplasmic reticulum in high-F groups II and III ultra-structurally. The results showed that excess dietary F in the range of 400-1200 mg/kg caused histological lesions, G₀/G₁ arrest and cellular apoptosis in the thymus, which inhibited the development of thymus and finally led to impaired cellular immune function.