Morphology of the chronic toxicity of busulfan on the islets of Langerhans in the rat.

Male Wistar rats were fed Busulfan dissolved in fat milk at a daily dose of 0.35, 0.89, 1.20 mg/kg body weight for a period of four, eight and twelve weeks. Examination by light microscopy, including immunohistochemistry, and by electron microscopy revealed changes in the pancreatic islets which were dependent on dose and time. First, hyperaemia was demonstrated, then perivascular "inbleedings" were followed by organisation and islet fibrosis with centripetal reduction of the islet cells. This resulted in an almost complete loss of A-cells and a reduction in the number of B-cells. A morphological factor analysis suggested additional analogies to type I - diabetes mellitus, so that for the formal pathogenesis, islet haematoma and immunological events have to be discussed.