Abstract
The time course of BCNU-induced hepatotoxicity was studied in rats for up to 4 months after single p.o. doses. Hepatic function was assessed by a series of standard techniques. By 1 week all doses of BCNU prolonged pentobarbital hypnosis and sulfobromophthalein retention. Later, elevations in serum bilirubin appeared, but these were delayed by as long as 63 days at the lowest dose. Serum bilirubin was direct-reacting at early stages but later shifted to indirect-reacting coincidental with a reduction of sulfobromophthalein retention. Histopathologic study revealed early pericholangitis and necrosis of bile ductules. Later, biliary hyperplasia and cirrhosis developed. These findings disclose a unique ability of BCNU to produce a prolonged and progressive bimodal toxicity resulting in hyperbilirubinemia.
Footnotes
- Received August 8, 1968.
- Accepted October 29, 1968.
- © 1969, by The Williams & Wilkins Company
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