To clarify the involvement of apoptosis in the immunotoxicity of
organotin compounds, we examined the induction of apoptosis in the peripheral lymphocytes and thymus of mice treated with
triphenyltin (
TPT),
tributyltin (TBT) or
dexamethasone (Dex). Application of
TPT or TBT and Dex resulted in a transient reduction in peripheral lymphocytes at 3 to 6 hr, and thymus
atrophy was observed at 6 and 24 hr after administration. Lymphocyte subpopulation analysis showed that
TPT and TBT induced a greater reduction in B cells than in T cells. The maximum levels of organotin in the blood were about 450 ng
TPT/ml in the
TPT-treated mice, and 170 ng TBT/ml in the TBT-treated mice. When the isolated peripheral lymphocytes were incubated with the organotins at 500 ng/ml,
TPT and TBT induced
necrosis in over 70% of cells, while both organotins caused lower percentages of apoptosis as well as
necrosis after 3 hr at 100 ng/ml. In the thymus, although in vivo treatment of mice with Dex caused apoptosis, neither apoptotic nor necrotic thymocytes were observed in the
TPT- and TBT-treated mice, indicating that the thymus
atrophy might be caused by the antiproliferative effects of these
organotin compounds. Thus, our results did not support the idea that apoptosis played a decisive part in the immunotoxicity of the
organotin compounds in vivo.