Rat urinary bladder epithelial lesions induced by acrolein.

Acrolein, a constituent of cigarette smoke and a metabolite of cyclophosphamide, has been shown to induce acute cytotoxicity of the rat urinary bladder mucosa when instilled directly into the bladder lumen. To evaluate the effects of systemic administration, we examined the rat urinary bladder following intragastric or intraperitoneal administration of acrolein to male F344 rats. In an initial experiment, acrolein was administered at a dose of 25 mg/kg, which proved to be extremely toxic. Five of 12 rats injected intragastrically and 5 of 12 injected intraperitoneally died within 24 hrs. After 2 days, 3 of the 3 surviving rats injected intraperitoneally had focal simple hyperplasia of the urinary bladder. None of the rats injected intragastrically had bladder hyperplasia. In a second experiment, acrolein was administered by intraperitoneal injection at doses of 0.5, 1, 2, 4, and 6 mg/kg. Five days later, the labeling index of the bladder mucosa was evaluated by autoradiography. In rats injected with 6 mg/kg of acrolein, the labeling index was significantly increased compared to the other doses and compared to a vehicle injection control group. These data indicate that sufficient acrolein reaches the urinary bladder to induce a proliferative response following intraperitoneal administration.