Studies on the mechanism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-induced hepatotoxicity - III. Ultrastructural characterization of bile duct injury

N. W. Kretschmer, P. J. Boor, R. A. el Azhary, A. E. Ahmed, E. S. Reynolds

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The antineoplastic nitrosourea CCNU is a known hepatotoxin which has been shown to cause hyperbilirubinemia and reduction in bile flow. We studied morphological alterations in the common bile duct and interlobular bile ducts at 6, 12, and 24 h in male rats given a single oral dose (50 mg/kg) of CCNU. The portal vein was perfused with 1.0% glutaraldehyde fixative. Portal areas and the common bile duct were selectively dissected and processed using standard methods for light and transmission electron microscopy. The epithelial cells of larger common bile duct and interlobular bile ducts showed increased rough endoplasmic reticulum, markedly increased free ribosomes, and mitochondrial degeneration at 6 and 12 h after CCNU. There was also bile imbibition and loss of microvilli, which increased in severity at 12 and 24 h. The interstitium showed infiltration by acute inflammatory cells and dilated capillaries at 6 h. By 24 h, degeneration of epithelial cells was extensive; cells became necrotic and sloughed into the duct lumen. The smaller bile ductules showed no significant degenerative changes; adjacent hepatocytes were unremarkable. Early CCNU injury appears localized in the large bile ducts and reflects inflammatory edema, bile stasis, and degeneration of epithelial cells. Our studies suggest that this ductal injury may reflect metabolism of CCNU to reactive species within the bile ducts.

Original languageEnglish (US)
Pages (from-to)109-117
Number of pages9
JournalCancer Chemotherapy and Pharmacology
Volume19
Issue number2
DOIs
StatePublished - Apr 1987

Fingerprint

Bile Ducts
Bile
Ducts
Common Bile Duct
Epithelial Cells
Wounds and Injuries
Fixatives
Hyperbilirubinemia
Rough Endoplasmic Reticulum
Glutaral
Microvilli
Portal Vein
Transmission Electron Microscopy
Antineoplastic Agents
Hepatocytes
Edema
Light
Infiltration
Metabolism
Rats

ASJC Scopus subject areas

  • Pharmacology
  • Oncology
  • Cancer Research

Cite this

Studies on the mechanism of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU)-induced hepatotoxicity - III. Ultrastructural characterization of bile duct injury. / Kretschmer, N. W.; Boor, P. J.; el Azhary, R. A.; Ahmed, A. E.; Reynolds, E. S.

In: Cancer Chemotherapy and Pharmacology, Vol. 19, No. 2, 04.1987, p. 109-117.

Research output: Contribution to journalArticle

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