Cytologic effects of Thiotepa and Adriamycin on normal canine urothelium

An experimental investigation was carried out to produce and observe controlled, sequential changes in normal bladder urothelium of female dogs caused by Thiotepa (triethylene thiophosphoramide) and Adriamycin (doxorubicin hydrochloride). Thiotepa (30 mg in 30 ml saline) was instilled for two hours into the bladders of five dogs at weekly intervals, and Adriamycin (1 ml/kg body weight) was given intravenously to five dogs at weekly intervals for a period of ten weeks. Control animals underwent only bladder irrigation with saline. Periodic catheterized urine and saline bladder irrigations and bladder biopsy specimens were obtained. After the tenth week all dogs were killed and autopsies conducted. Major observations in the experimental animals included cellular enlargement, bizarre cell shapes, cytoplasmic vacuolization, nuclear and nucleolar enlargement, multinucleation, pyknosis, karyorrhexis and infiltration by neutrophilic leukocytes. In some animals, reversion to a normal cytologic pattern occurred in the ten-week period. The application of these observations to human urinary cytopathology is discussed.