Related Experiment Video

Updated: Sep 30, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
07:38

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

Published on: September 25, 2017

[Accelerated microsomal DNA synthesis under the influence of xenobiotics and chemical carcinogens]

M I Lerman, O Iu Abakumova, N G Kutsenko

    Biokhimiia (Moscow, Russia)
    |April 1, 1979
    PubMed

    Insights

    Chemicals like methyl nitrosourea stimulate liver microsomal DNA synthesis, independent of nuclear DNA and mitochondrial DNA synthesis. This suggests a unique role for microsomal DNA in response to xenobiotics.

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Toxicology

    Context:

    • Liver DNA synthesis is crucial for cellular function and response to external stimuli.
    • Carcinogens and other chemicals can disrupt normal DNA synthesis pathways.
    • Microsomal DNA synthesis represents a less understood aspect of cellular response.

    Purpose:

    • To investigate the effect of specific chemical agents (3,4-benz(a)pyrene, methyl nitrosourea, phenobarbital) on liver DNA synthesis in mice.
    • To determine the relationship between microsomal DNA synthesis and nuclear/mitochondrial DNA synthesis.
    • To explore the potential role of microsomal DNA in response to xenobiotic exposure.

    Summary:

    • Injection of 3,4-benz(a)pyrene, methyl nitrosourea, and phenobarbital induced a significant increase in [14C]-thymidine incorporation into liver microsomal DNA, while suppressing nuclear DNA synthesis.
    • Microsomal DNA synthesis was unaffected by inhibitors of nuclear DNA synthesis (cycloheximide, puromycin) and was independent of nuclear and mitochondrial DNA synthesis, as shown by hydroxyurea treatment.
    • The stimulation of microsomal DNA synthesis by these agents was not solely due to DNA repair mechanisms, suggesting a distinct pathway.

    Impact:

    • Findings indicate that liver microsomal DNA synthesis is an independent system, potentially playing a role in cellular defense against xenobiotics.
    • This research highlights a novel mechanism of DNA synthesis regulation in response to chemical exposure.
    • The study provides a foundation for further investigation into the specific functions and metabolic stability of microsomal DNA.

    More Related Videos

    Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling09:33

    Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

    Published on: March 20, 2018

    Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter12:15

    Quantification of three DNA Lesions by Mass Spectrometry and Assessment of Their Levels in Tissues of Mice Exposed to Ambient Fine Particulate Matter

    Published on: May 29, 2019

    Related Concept Videos

    Mutations02:27

    Mutations

    Mutations are changes in the sequence of DNA. These changes can occur spontaneously during DNA replication or be induced by environmental factors. Mutations can be characterized in several ways: by whether and how they alter the amino acid sequence of the protein, by the scale of the DNA affected, and by whether they affect somatic or germline cells.Consequences of Point Mutations at the Molecular LevelMutations that affect a single nucleotide are called point mutations. When point mutations...
    Mutations01:35

    Mutations

    Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
    Chromosomal Alterations Are Large-Scale Mutations
    While point mutations are changes in a single nucleotide in...
    Nucleotide Excision Repair01:38

    Nucleotide Excision Repair

    DNA Distortion and Damage
    Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
    Mutagenicity and Carcinogenicity01:25

    Mutagenicity and Carcinogenicity

    Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
    Bioactivation and Tissue Toxicity01:25

    Bioactivation and Tissue Toxicity

    Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
    Spontaneous and Induced Mutations01:30

    Spontaneous and Induced Mutations

    Spontaneous mutations arise infrequently during DNA replication due to errors in the process. A key factor behind these errors is tautomeric shifts in nitrogenous bases, where bases transition from keto to enol forms or amino to imino forms. This shift can alter base-pairing rules, leading to mutations. Additionally, reactive oxygen species (ROS) arising from aerobic metabolism can damage DNA, resulting in depurination (loss of a purine base) or depyrimidination (loss of a pyrimidine base).