In vivo effects of mercury (II) on deoxyuridine triphosphate nucleotidohydrolase, DNA polymerase (alpha, beta), and uracil-DNA glycosylase activities in cultured human cells: relationship to DNA damage, DNA repair, and cytotoxicity.
The effect of mercuric acetate on the activities of deoxyuridine triphosphate nucleotidohydrolase (dUTPase), DNA polymerase (alpha, beta), and uracil-DNA glycosylase has been studied in cultured human KB cells. There was a dose- and time-dependent inactivation of both dUTPase and DNA polymerase alpha activities by mercuric acetate. In cells exposed to low concentrations (10 microM) of mercuric acetate, dUTPase was most sensitive to inhibition with 30% of the activity being inhibited after a 1-hr exposure. At higher concentrations or for longer exposure times, DNA polymerase alpha was most sensitive to inhibition with greater than 60% of the activity being inhibited by 25 microM mercuric acetate after a 15-min exposure. There was no inhibition of DNA polymerase beta or uracil-DNA glycosylase activities in cells exposed to 50 microM mercuric acetate for 90 min. In fact, there was a time- and dose-dependent activation of uracil-DNA glycosylase activity with maximum activation occurring in cells exposed to 50 microM mercuric acetate. The inhibition of dUTPase and DNA polymerase alpha activities and the activation of uracil-DNA glycosylase activity correlated with the induction of single-strand breaks in DNA by mercuric acetate and with the decrease in cell viability.
D002413:Cations, Divalent; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004249:DNA Damage; D045647:DNA Glycosylases; D004256:DNA Polymerase I / Q000378:metabolism; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004260:DNA Repair / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008628:Mercury / Q000633:toxicity*; D009699:N-Glycosyl Hydrolases / Q000378:metabolism*; D019384:Nucleic Acid Synthesis Inhibitors; D014176:Protein Biosynthesis; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors*; D051981:Uracil-DNA Glycosidase
D002413:Cations, Divalent; D019384:Nucleic Acid Synthesis Inhibitors; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases; D051981:Uracil-DNA Glycosidase; D011755:Pyrophosphatases; C020020:dUTP pyrophosphatase; D008628:Mercury