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Organ specific acute toxicity of the carcinogen trans-4-acetylaminostilbene is not correlated with macromolecular

A Pfeifer, H G Neumann

    Chemico-Biological Interactions
    |September 1, 1986
    PubMed

    Insights

    trans-4-Acetylaminostilbene (trans-AAS) causes acute stomach toxicity in rats. This toxicity is not due to reactive metabolites but rather the parent compound accumulating in the stomach.

    Area of Science:

    • Toxicology
    • Pharmacology
    • Gastroenterology

    Background:

    • trans-4-Acetylaminostilbene (trans-AAS) is known to cause acute toxicity in rats, specifically targeting the glandular stomach.
    • Previous studies indicated that methylcholanthrene (MC) pretreatment prevents this toxicity, suggesting a role for reactive metabolites.

    Purpose of the Study:

    • To investigate the mechanism of trans-4-Acetylaminostilbene (trans-AAS) induced glandular stomach toxicity.
    • To determine if toxicity is mediated by reactive metabolites or the parent compound.

    Main Methods:

    • Oral administration of trans-[3H]-AAS to Wistar rats under different pretreatment conditions (phenobarbital, methylcholanthrene).
    • Measurement of covalent binding of trans-AAS to macromolecules (proteins, RNA, DNA) in various tissues.
    • Assessment of tissue concentrations and stomach function.

    Main Results:

    • Macromolecular binding of trans-AAS was lower in the target glandular stomach compared to liver and kidney.
    • Methylcholanthrene pretreatment reduced binding in extrahepatic tissues but not in the liver.
    • The glandular stomach showed a high affinity for the parent trans-AAS compound, with high concentrations observed early in poisoning.

    Conclusions:

    • The glandular stomach toxicity of trans-4-Acetylaminostilbene (trans-AAS) is not caused by tissue-specific metabolic activation.
    • The parent compound's accumulation in the glandular stomach is the likely cause of toxicity.
    • Stomach impairment and high parent compound concentrations are key factors in trans-AAS poisoning.

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