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Updated: Aug 18, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
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A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

Published on: September 25, 2017

The nature of microsomal N-nitrosodimethylamine demethylase and its role in carcinogen activation

J Hong, C S Yang

    Carcinogenesis
    |December 1, 1985
    PubMed

    Insights

    N-nitrosodimethylamine (NDMA) demethylase in rat liver microsomes activates NDMA. Enzyme induction enhances DNA methylation in vitro and in vivo at high NDMA doses.

    Area of Science:

    • Hepatology
    • Toxicology
    • Enzymology

    Background:

    • N-nitrosodimethylamine (NDMA) is a potent carcinogen requiring metabolic activation.
    • Understanding the enzymes involved in NDMA activation is crucial for assessing its toxicological risks.

    Purpose of the Study:

    • To investigate the subcellular localization and role of NDMA demethylase in rat liver cells.
    • To determine the relationship between NDMA demethylase activity and DNA methylation by NDMA.

    Main Methods:

    • Enzyme activity was localized to the microsomal fraction of rat liver cells.
    • DNA alkylation was quantified by measuring O6-methylguanine and 7-methylguanine using HPLC and fluorescence detection.
    • NDMA demethylase activity was induced by various agents (isopropanol, ethanol, acetone, fasting) and its effect on DNA methylation was assessed in vitro and in vivo.

    Main Results:

    • NDMA demethylase activity was predominantly found in liver microsomes, correlating with NDMA's conversion to alkylating species.
    • Induction of microsomal NDMA demethylase activity by ethanol, isopropanol, acetone, and fasting increased in vitro DNA methylation by NDMA.
    • Ethanol pretreatment enhanced in vivo DNA alkylation by NDMA at a high dose (75 mg/kg) but not at lower doses (≤25 mg/kg).

    Conclusions:

    • NDMA demethylase, primarily located in liver microsomes, plays a key role in activating NDMA.
    • Enzyme induction significantly enhances NDMA-induced DNA methylation, particularly at higher exposure levels.
    • These findings highlight the importance of NDMA demethylase in mediating NDMA's genotoxicity.

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