A marked dose dependent reduction in thymus weight and its nucleated cell counts with histological alterations was observed in rats exposed to oral
dibutyltin dilaurate (DBTL) for 2 weeks at 2, 4, 8 or 16 mg/kg
body weight. The incorporation of [3H]-
inositol into all the three major
phosphoinositides was drastically reduced in thymocytes in a dose dependent manner. Furthermore, the basal and the
mitogen (Con A) stimulated [3H]-
inositol phosphates generation was diminished significantly in 8 mg DBTL group. However, in vitro incubation of DBTL with thymocytes failed to evoke any change in
phosphoinositide hydrolysis. Similarly, a time and dose dependent inhibition in
phosphoinositide synthesis with as high as 80% by 10 microM DBTL was exhibited under in vitro conditions.
A 130% and 600% enhancement of
protein kinase C (PKC) activity in thymocytes was seen in 4 mg and 8 mg DBTL group, respectively. Addition of DBTL to the cell free assay system of thymocytes resulted in a concentration dependent activation of the
enzyme activity. A dose dependent increase in intracellular
calcium was also evident when DBTL was added to thymocytes under in vitro conditions. These results are of significance and may bear close relationship to the observed thymic
atrophy by DBTL.