On the mechanism of dialkyltin-induced thymus involution.
In relation to the thymolytic activity of dialkyltin compounds, the effects of di-n-butyltin (DBTC) and di-n-octyltin dichloride (DOTC) on the ultrastructure of the rat thymus, the proliferation of bone marrow stem cells and their interference with growth hormone production are analyzed. Ultrastructurally, depletion of small lymphocytes in the thymic cortex, without signs of lymphocyte destruction or macrophage activation, was the most prominent feature of DOTC treatment. The thymus cortex was maximally depleted 96 h after a single i.p. injection of 1 mg DOTC/kg body weight. 120 h after DOTC treatment a repopulation of the cortex with small lymphocytes was noted together with the presence of many pale large nuclei of large lymphocytes, suggestive of active blast transformation. These thymus effects are probably not caused by a diminished input of bone marrow stem cells into the thymus, since neither the spontaneous blastogenesis nor the colony formation of bone marrow cells isolated from DBTC-treated animals were affected. An indirect mechanism of thymus involution induced by interference with the hormonal system is also very unlikely. A stress-related increase of glucocorticosteroids by dialkyltins has already been excluded (Seinen and Willems, 1976). An interference of dialkyltins with growth hormone production, as indicated in this study, did not occur. Application of growth hormone in amounts that reversed the hypophysectomy-induced thymus atrophy did not modify the thymus involution induced by DOTC treatment of rats. However, an interference with the production of thymic humoral factors cannot be excluded yet, although it is not supported by morphological changes in thymic reticular cells. Only an increased vacuolization of reticular epithelial cells is seen when the thymus is markedly involuted, but this is considered to be a consequence rather than a cause of thymus atrophy. Most probably the dialkyltin-induced thymus involution is caused by an antiproliferative activity, which is strongly supported by an inhibition of thymidine incorporation of thymocytes isolated from DBTC-treated rats.
D000818:Animals; D001284:Atrophy; D001853:Bone Marrow / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000096:biosynthesis / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009947:Organotin Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure
D009947:Organotin Compounds; D013006:Growth Hormone; C020735:dibutyldichlorotin; C020297:di-n-octyltin dichloride