Cellular and molecular effects of di-n-octyltin dichloride on the rat thymus.

ABSTRACT

Experiments have been performed to characterise early changes in the proliferative capacity and phenotypic makeup of thymocytes obtained from DOTC-treated PVG rats. The analysis of density gradient-separated thymocytes demonstrated that within 72 h of oral dosing, spontaneous in vitro thymocyte proliferation was markedly suppressed. A concomitant depletion of an MRC OX18 positive thymocyte population was also observed. These events occurred prior to both overt thymic weight loss and characteristic, treatment-induced histopathological changes. Since recent evidences suggest that the growth factor interleukin-2 (IL-2) may play an important role in thymocyte proliferation, additional molecular biological studies were performed to evaluate whether DOTC may exert its anti-proliferative effects by compromising IL-2 production. Using a mRNA cytoplasmic dot blot technique, the examination of thymocyte lysates from treated and control animals revealed that DOTC markedly down regulated and at high doses abolished, the normal expression of the IL-2 gene. The high turnover gene alpha-actin was, however, unaffected by its action, thus demonstrating the selective effects of DOTC.