Very low concentrations of arsenite suppress poly(ADP-ribosyl)ation in mammalian cells.
Arsenite is a naturally occurring environmental pollutant of major concern, since adverse health effects including cancer of skin and internal organs have been attributed to chronic arsenic exposure especially via drinking water. Arsenite is not a significant inducer of point mutations but exerts clastogenic activities and interferes with various DNA repair systems at concentrations in the low micromolar range. Nevertheless, no single DNA repair protein exquisitely sensitive to arsenic has been identified. Here we report that poly(ADP-ribosyl)ation, which is predominantly mediated by poly(ADP-ribose) polymerase-1 (PARP-1), is inhibited at concentrations as low as 10 nM in cultured HeLa cells, closely matching arsenic concentrations in blood and urine of the general population. Since poly(ADP-ribosyl)ation is an immediate cellular response to DNA damage, playing a major role in DNA base excision repair and the maintenance of genomic stability, its inhibition by arsenite may add to the risk of cancer formation under low-exposure conditions.
Hartwig
Andrea
A
Universität Karlsruhe, Institut für Lebensmittelchemie und Toxikologie, Karlsruhe, Germany. Andrea.Hartwig@chemie.uni-karlsruhe.de
Pelzer
Anke
A
Asmuss
Monika
M
Bürkle
Alexander
A
D018053:Arsenites / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000494:pharmacology*; D006031:Glycosylation; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D009153:Mutagens / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011499:Protein Processing, Post-Translational / Q000187:drug effects*
D018053:Arsenites; D004273:DNA, Neoplasm; D004785:Environmental Pollutants; D009153:Mutagens; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011064:Poly Adenosine Diphosphate Ribose; D006861:Hydrogen Peroxide; C015001:arsenite