The in vitro influence of sulfated bislactobionic acid amides on O6-alkylguanine-DNA alkyltransferase, DNase I, nucleic acid synthesis and chromatin structure

Abstract

The influence of four sulfated bis-lactobionic acid amides (BLAA) of molecular weights between 2388 and 2514 on O 6-alkylguanine-DNA alkyltransferase (AT), DNase I and nucleic acid synthesis as well as on nucleoid sedimentation and the viscosity of alkaline lysates of chicken embryo cells was studied in vitro. The activities of AT and DNase I were inhibited by BLAA in a dose-dependent manner. Depending on the polyanion used, concentrations depleting AT activity by 50% ranged between 3.5 and 7.0 μM, whereas BLAA concentrations of almost 250–320 μM were needed to halve DNase I activity. At concentrations above 8 μM, BLAA decreased scheduled DNA synthesis in a dose-dependent fashion whereas RNA synthesis remained unchanged even at the highest BLAA concentrations used (2 mM). In chicken embryo brain cells BLAA exerted a biphasic effect on the nucleoid sedimentation and the viscosity of alkaline cell lysates reflecting a decrease in chromatin compactness at lower BLAA concentrations (10–100 μM) and an increase in chromatin compactness at higher polyanion concentrations (≥200 μM). The remarkably high sensitivity of the nuclear enzyme AT deserves further investigation in regard to the fate of the polyanions within cells and tissues.