Morphological and biochemical changes in the liver of various species in experimental phospholipidosis after diethylaminoethoxyhexestrol treatment.

The mechanism of druginduced experimental phospholipidosis was studied in several species by the administration of diethylaminoethoxyhexestrol. Rabbits, rats, mice, dogs, and guinea pigs developed microscopic and biochemical abnormalities, while hamsters were less affected. In the liver of affected species characteristic subcellular changes were found, accompanied by phospholipid accumulation. Hepatic lesions consisted of concentric lamellar bodies with varying degrees of osmic affinity, representing secondary lysosomes characterized by cytochemical methods. Accumulation of these bodies was also seen in Kupffer, endothelial, and biliary epithelial cells. The intensity of the changes was related to species susceptibility. Biochemical studies revealed an overall increase of total phospholipids in the affected species, together with changes in the relative distribution of individual phospholipids and the appearance of unidentified components. The activity of microsomal drug metabolizing enzymes and microsomal phospholipid synthesis were diminished. The lesions closely resembled those observed in man after treatment with diethylaminoethoxyhexestrol and are related to altered phospholipid metabolism with subsequent changes in microsomal drug metabolizing enzyme activity.