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Journal of Pharmacology And Experimental Therapeutics, Vol. 166, Issue 1, 104-112, 1969
Copyright © 1969 by American Society for Pharmacology and Experimental Therapeutics

THE HEPATOTOXICITY OF 1,3-BIS(2-CHLOROETHYL)-1-NITROSOTJREA (BCNU) IN RATS

GEORGE R. THOMPSON 1 and ROBERT E. LARSON 1

1 Department of Pharmacology, School of Pharmacy, Oregon State University, Corvallis, Oregon

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.

Submitted on August 8, 1968
Accepted on October 29, 1968




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Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics.