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.
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Authors | E Chieli, M Saviozzi, G Malvaldi |
Journal | Archives of toxicology
(Arch Toxicol)
Vol. 61
Issue 2
Pg. 150-4
(Dec 1987)
ISSN: 0340-5761 [Print] Germany |
PMID | 3439887
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amides
- Thioamides
- thiobenzamide
- DNA
- Cytochrome P-450 Enzyme System
- Mixed Function Oxygenases
- NADH Dehydrogenase
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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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