Toxic effects of bis (tributyltin) oxide on the synthesis and secretion of zymogen granules in the rat exocrine pancreas.

Toxic effects of bis (tributyltin) oxide (TBTO) on the rat exocrine pancreas were studied with an electron microscope and X-ray microanalyzer. To measure tin concentrations in the blood, atomic absorption spectrophotometry was carried out. Adult male Wistar rats received an intramuscular injection of TBTO (0.5 ml/kg). At 2 h after injection, a marked swelling of mitochondria and an enlargement of the cisterns of the rough endoplasmic reticulum appeared in the pancreatic acinar cells. Using X-ray microanalysis, tin peaks were preferentially obtained from the swollen mitochondria. Heterogeneous zymogen granules with an electron dense core and a pale central zone increased in number in the acinar cells between 4 and 8 h after TBTO treatment. By 24 h after TBTO injection, the acinar cells had been ultrastructurally restored. Atomic absorption analyses showed that blood tin concentrations peaked at approximately 1 h after TBTO injection and then progressively declined, reaching the zero level at 12 h after injection. The effects of TBTO on the synthesis and secretion of zymogen granules were investigated with and without caerulein as a stimulant of secretion. Data obtained from these experiments indicated that TBTO inhibited both the synthesis and secretion of zymogen granules. The inhibition of the protein synthesis and secretion might be caused partly by mitochondrial dysfunctions due to the toxic effects of TBTO.