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Nitrosocarbaryl: its effect on human DNA

J D Regan, R B Setlow, A A Francis

    Mutation Research
    |August 1, 1976
    PubMed
    Summary
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    Nitrosocarbaryl, a pesticide derivative, causes DNA damage in human skin cells, specifically single-strand breaks. This damage, linked to a methyl residue, persists for up to 20 hours after exposure.

    Area of Science:

    • Environmental toxicology
    • Molecular toxicology
    • Human cellular responses

    Background:

    • Carbaryl is a widely used agricultural pesticide.
    • Understanding the genotoxicity of pesticide derivatives is crucial for human health risk assessment.

    Purpose of the Study:

    • To investigate the DNA damaging effects of carbaryl and its derivative, nitrosocarbaryl, on human skin cells.
    • To elucidate the mechanism of DNA interaction by nitrosocarbaryl.

    Main Methods:

    • Treatment of normal and xeroderma pigmentosum human skin cells with carbaryl and nitrosocarbaryl.
    • Alkaline sucrose gradient sedimentation to detect DNA strand breaks.
    • Cesium chloride density gradient centrifugation of radiolabeled DNA to identify interacting residues.

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    Main Results:

    • Nitrosocarbaryl induced numerous DNA single-strand breaks in human cells, while carbaryl did not.
    • The DNA-damaging effects of nitrosocarbaryl were observable for up to 20 hours post-treatment.
    • Radiolabeling studies indicated that a methyl-containing residue of nitrosocarbaryl irreversibly binds to human DNA.

    Conclusions:

    • Nitrosocarbaryl is genotoxic to human skin cells, causing DNA strand breaks.
    • The genotoxicity is mediated by the irreversible binding of a methyl residue from the nitrosocarbaryl molecule.
    • These findings highlight the potential risks associated with nitrosocarbaryl exposure and its mechanism of DNA interaction.