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Changes in the rat liver drug metabolizing system during a short thiobenzamide feeding cycle.

Abstract
The changes in the hepatic drug metabolizing enzymes induced by the liver tumor promoter thiobenzamide (TB) were investigated. Feeding of TB to rats at a promoting regimen (1 g/kg of diet for 2 weeks) resulted in a significant decrease in the amount of liver microsomal cytochrome P-450 and of total heme. Also, the activity of cytochrome P-450 dependent monooxygenases (aminopyrine demethylase, arylhydrocarbonmonooxygenase and ethoxycoumarindeethylase) and FAD-containing monoxygenase (N,N-dimethylaniline N-oxidase and TB S-oxidase) were depressed. By contrast, phase II enzymes such as epoxide hydrase, UDP-glucuronyl transferase and GSH-transferase were significantly induced. This overall change in the drug metabolizing system was associated with tolerance of the liver towards a high necrogenic dose of TB itself as well as with an increase of mitoses and apoptosis of the hepatocytes. The findings suggest a possible relationship between this TB-induced adaptive response and the promoting activity of the compound on liver carcinogenesis.
AuthorsE Chieli, M Saviozzi, G Malvaldi
JournalArchives of toxicology (Arch Toxicol) Vol. 61 Issue 2 Pg. 150-4 (Dec 1987) ISSN: 0340-5761 [Print] Germany
PMID3439887 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amides
  • Thioamides
  • thiobenzamide
  • DNA
  • Cytochrome P-450 Enzyme System
  • Mixed Function Oxygenases
  • NADH Dehydrogenase
Topics
  • Adaptation, Biological (drug effects)
  • Amides (toxicity)
  • Animals
  • Body Weight (drug effects)
  • Cytochrome P-450 Enzyme System (metabolism)
  • DNA (metabolism)
  • Liver (enzymology, metabolism)
  • Male
  • Mitosis (drug effects)
  • Mixed Function Oxygenases (metabolism)
  • NADH Dehydrogenase (metabolism)
  • Organ Size (drug effects)
  • Rats
  • Rats, Inbred Strains
  • Thioamides (toxicity)

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