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PubMed · 8765144

Ataxia telangiectasia heterozygotes and patients display increased fluidity and decrease in contents of sulfhydryl groups in red blood cell membranes.

M Rybczyńska·A L Pawlak·E Sikorska·R Ignatowicz
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Abstract

In red blood cell membranes of ataxia telangiectasia mutated (ATM) homozygotes and heterozygotes, decreased values of the corrected fluorescence anisotropy and the anisotropy parameter were found, indicating increased fluidity and decreased microviscosity, respectively. These changes in membranes were accompanied by a decrease in SH-groups and an increase in malondialdehyde (MDA) contents. The content of MDA both in homozygotes and in heterozygotes exceeded roughly threefold the respective control values. Decreased content of GSH in red blood cells was found only in ATM homozygotes. The change most specific for the ATM gene appears to be the increase in fluidity, since only this parameter displays the proportionally greater changes in ATM homozygotes compared to ATM heterozygotes. The observations presented here may indicate that the ATM gene is expressed in precursors of red blood cells and deficiency of normal AT gene function may produce the changes which persist in circulating cells.

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Ataxia TelangiectasiaChildDiphenylhexatrieneErythrocyte MembraneFluorescence PolarizationFluorescent DyesGlutathioneHeterozygoteHumansLipid PeroxidationMalondialdehydeMembrane FluiditySulfhydryl CompoundsViscosityJournal ArticleResearch Support, Non-U.S. Gov't

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M Rybczyńska, A L Pawlak, E Sikorska, R Ignatowicz. 1996-08-16. Ataxia telangiectasia heterozygotes and patients display increased fluidity and decrease in contents of sulfhydryl groups in red blood cell membranes.. https://doi.org/10.1016/0005-2760(96)00067-7

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Radiation induction of p53 in cells from Nijmegen breakage syndrome is defective but not similar to ataxia-telangiectasia.

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Sister chromatid exchanges and DNA topoisomerase II inhibitors: effect of low concentrations of etoposide (VP-16) in ataxia telangiectasia lymphoblastoid cell lines.

The correlation between etoposide (VP-16) cytotoxicity and the induction of sister chromatid exchanges (SCEs) suggested that the promotion of DNA recombination events may be crucial for the activity of antitopoisomerase drugs. To further evaluate this hypothesis, we investigated the correlation between VP-16 induction of SCEs, chromosomal aberrations and cell cycle alterations in lymphoblastoid cell lines derived from patients affected by ataxia telangiectasia (AT), whose cells are known as hypersensitive to the cytotoxic and clastogenic activity of DNA topoisomerase II inhibitors. Our present study has shown that AT homozygous and heterozygous cell lines exposed to low VP-16 concentrations, although hypersensitive to the induction of chromosomal aberrations, exhibit an induction of SCEs comparable to that found in normal cell lines. Moreover, while the clastogenic effect of the drug was directly correlated to the reduction of the mitotic index, the enhancement of SCE frequencies, obtained over the same range of VP-16 concentrations, was not paralleled by a modification of proliferation index. Thus, these results suggest that etoposide retains in AT cells a strong clastogenic and cytostatic activity which is independent from DNA recombination events and which may be important for the induction of cell death by this kind of drug.

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