O6-alkylguanine-DNA alkyltransferase, DNase I, nucleic acid synthesis and nucleoids in vitro under the influence of pentosan polysulfate.
The in vitro influence of pentosan polysulfate (CAS 116001-96-8, PPS) on DNase I activity as well as on O6-alkylguanine-DNA alkyltransferase (AT), nucleic acid synthesis, nucleoid sedimentation and viscosity of alkaline lysates of chicken embryo brain cells was studied. PPS inhibited the activities of AT and DNase I in a dose-dependent manner, with ED50 values being about 13 and 380 micrograms/ml. Scheduled DNA synthesis was depleted by PPS. The ED50 values ranged between 45 and 55 micrograms PPS/ml. A slight increase in RNA synthesis could be observed at polyanion concentrations of 28-112 micrograms/ml. Nucleoid sedimentation and viscosity of alkaline cell lysates reflected a decrease in chromatin compactness at lower (7-25 micrograms/ml) and an increase in chromatin compactness at higher (> or approximately = 112 micrograms/ml) PPS concentrations. From the present results it is concluded that PPS, at clinically relevant concentrations, is able to interact in vitro with enzyme systems being critical to important nuclear functions. The remarkably high sensitivity of the nuclear enzyme AT deserves further investigations with regard to a possible synergism of polyanions and chemotherapeutically used alkylating agents.
Tempel
K
K
Institute of Pharmacology, Toxicology and Pharmacy, University of Munich, Germany.
Schleifer
S
S
D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology; D002642:Chick Embryo; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D003850:Deoxyribonuclease I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009696:Nucleic Acids / Q000096:biosynthesis*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology*; D011312:Pressure; D012313:RNA / Q000096:biosynthesis; D014783:Viscosity
D002843:Chromatin; D004791:Enzyme Inhibitors; D009696:Nucleic Acids; D010426:Pentosan Sulfuric Polyester; D012313:RNA; D004247:DNA; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; D003850:Deoxyribonuclease I