Organotin induced thymus atrophy and apoptosis.

Abstract

Oral administration of tributyltin chloride (TBTC) is known to cause thymus atrophy and suppression of the T-cell dependent immune responses. To study the mechanism underlying the thymus atrophy, induction of apoptosis was investigated. Oral administration of TBTC (100 mg /kg in NMF diet) enhanced the fragmentation of DNA in the thymus. Activation of DNase was observed along with the fragmentation of DNA. The apparent molecular mass of the DNase was 18 kDa, suggesting the activated DNase was NUC18. Activation of Caspase-3 was observed, indicating the activation of caspase cascade. In addition, FasL levels were increased in response to the administration of TBTC. Taken together, these data show that the induction of apoptosis in the thymus by the administration of TBTC is mediated by the FasL/Fas dependent pathway, which results in the activation of both Caspase cascade and DNase (NUC18).