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Cell killing by lysosomotropic detergents.

D K Miller, E Griffiths, J Lenard

    The Journal of Cell Biology
    |December 1, 1983
    PubMed
    Summary
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    Lysosomotropic detergents, like N-dodecylimidazole, kill cells by damaging lysosomes, causing leakage and cell death. Protecting lysosomes prevents this detergent-induced cell death.

    Area of Science:

    • Cell Biology
    • Biochemistry
    • Toxicology

    Background:

    • Lysosomotropic detergents are amines with hydrocarbon tails.
    • These compounds accumulate in lysosomes.
    • Their mechanism of cell killing was previously unclear.

    Purpose of the Study:

    • To elucidate the mechanism of cell killing by lysosomotropic detergents.
    • To investigate the role of lysosomes in this process.
    • To identify key events following detergent exposure.

    Main Methods:

    • Using lucifer yellow CH to label lysosomes and light microscopy.
    • Employing 3H-labeled N-dodecylimidazole to track cellular uptake and localization.
    • Measuring lysosomal pH changes and protein/RNA synthesis.

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  • Assessing cell viability and sensitivity at different cell densities.

    • Main Results:

    • N-dodecylimidazole rapidly damaged lysosomes, causing dye leakage and subsequent cell death.
    • The detergent was trapped in lysosomes, leading to sustained damage.
    • Cell killing showed sigmoidal dose-response curves and was density-dependent.
    • Lysosomal pH increased, followed by inhibition of synthesis and cell damage.
    • Agents that raised lysosomal pH protected cells from killing.

    Conclusions:

    • Lysosomotropic detergents kill cells by disrupting lysosomes from within.
    • Lysosomal damage is the primary event leading to cell death.
    • The findings support a model where intralysosomal events trigger toxicity.