The in vitro influence of sulfated bis-lactobionic acid amides on O6-alkylguanine-DNA alkyltransferase, DNase I, nucleic acid synthesis and chromatin structure.
The influence of four sulfated bis-lactobionic acid amides (BLAA) of molecular weights between 2388 and 2514 on O6-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 microM, whereas BLAA concentrations of almost 250-320 microM were needed to halve DNase I activity. At concentrations above 8 microM, 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 microM) and an increase in chromatin compactness at higher polyanion concentrations (> or = 200 microM). The remarkably high sensitivity of the nuclear enzyme AT deserves further investigation in regard to the fate of the polyanions within cells and tissues.
Ignatius
A
A
Institute of Pharmacology, Toxicology, University of Munich, F.R.G.
Meinetsberger
E
E
Raake
W
W
Tempel
K
K
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D002240:Carbohydrate Sequence; D002642:Chick Embryo; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors*; D004187:Disaccharides / Q000138:chemical synthesis / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D019853:O(6)-Methylguanine-DNA Methyltransferase; D012313:RNA / Q000096:biosynthesis*; D013498:Suramin / Q000494:pharmacology
D000925:Anticoagulants; D002843:Chromatin; D004187:Disaccharides; D013498:Suramin; D012313:RNA; D004247:DNA; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D003850:Deoxyribonuclease I; C069690:aprosulate