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Cellular abnormalities of folate deficiency.

S E Steinberg, S Fonda, C L Campbell

    British Journal of Haematology
    |August 1, 1983
    PubMed
    Summary
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    Folate deficiency in cells disrupts DNA synthesis and morphology. Sensitive indicators like DNA synthesis assays reveal abnormalities when folate levels drop below critical thresholds, impacting cell replication.

    Area of Science:

    • Cell Biology
    • Molecular Biology
    • Biochemistry

    Background:

    • Folate is essential for DNA synthesis and cell replication.
    • Folate deficiency can lead to various cellular abnormalities.
    • Understanding the precise thresholds for these abnormalities is crucial.

    Purpose of the Study:

    • To investigate the development of folate-deficiency abnormalities in Friend erythroleukaemia cells.
    • To identify sensitive indicators of folate deficiency related to DNA synthesis and morphology.
    • To determine the relationship between intracellular folate levels and cell replication capacity.

    Main Methods:

    • Friend erythroleukaemia cells were cultured with varying [3H]PteGlu1 concentrations and then transferred to folate-free media.
    • Intracellular folate levels, growth potential, morphology, deoxyuridine (dU) suppression, and DNA content via flow cytometry were analyzed.

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  • Statistical analysis was used to correlate intracellular folate levels with observed cellular changes.

    • Main Results:

    • DNA synthesis indicators (dU suppression and flow cytometry) were most sensitive to folate deficiency, showing abnormalities at intracellular folate levels of 0.2-0.5 ng/10(6) cells.
    • Morphological changes, such as megaloblastosis, occurred at lower folate levels (below 0.06 ng/10(6) cells).
    • Cell replication capacity in folate-free media was directly correlated with intracellular folate levels (r = 0.993).

    Conclusions:

    • Cellular stigmata of folate deficiency appear when intracellular folate falls below 3 X 10(5) molecules per cell, impacting DNA synthesis.
    • The capacity for cell replication is lost when folate levels drop below 7-10 X 10(5) molecules per cell.
    • Intracellular folate levels are critical predictors of early folate-deficiency defects and determine replicative potential.