Reduction in peripheral lymphocytes and thymus atrophy induced by organotin compounds in vivo.
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.
Ueno
Shunji
S
School of Veterinary Medicine, Kitasato University, Aomori, Japan. ueno@vmas.kitasato-u.ac.jp
Kashimoto
Takashige
T
Susa
Nobuyuki
N
Asai
Tomohito
T
Kawaguchi
Souta
S
Takeda-Homma
Shino
S
Terada
Yasuko
Y
Sugiyama
Masayasu
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001284:Atrophy; D003907:Dexamethasone / Q000633:toxicity; D005434:Flow Cytometry; D007700:Kinetics; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009947:Organotin Compounds / Q000097:blood* / Q000633:toxicity; D013950:Thymus Gland / Q000187:drug effects / Q000473:pathology*; D014220:Trialkyltin Compounds / Q000633:toxicity*
D009947:Organotin Compounds; D014220:Trialkyltin Compounds; C011559:tributyltin; D003907:Dexamethasone; C030665:triphenyltin