Inhibition of DNA polymerase from L1210 murine leukemia by a sulfhydryl reagent from agaricus bisporus.
The 490 quinone, a natural sulfhydryl-arylating reagent from the mushroom, Agaricus bisporus, markedly inhibited L1210 murine leukemia DNA polymerase alpha while resulting in little inhibition of DNA polymerase beta from this source. This quinone was more strongly inhibitory than p-chloromercuri-benzoate or N-ethylmaleimide and was less readily neutralized by sulfhydryl-containing molecules such as dithioerythritol. Preliminary experiments indicate that DNA protects DNA polymerase alpha from inhibition by the 490 quinone. The inhibition of DNA synthesis by quinone 490 may contribute significantly to the cytotoxicity of this compound and to the potential of gamma-L-glutaminyl-4-hydroxybenzene as an antitumor agent.
D000818:Animals; D000970:Antineoplastic Agents; D001665:Binding Sites; D002729:Chloromercuribenzoates / Q000494:pharmacology; D004256:DNA Polymerase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004229:Dithiothreitol / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D005033:Ethylmaleimide / Q000494:pharmacology; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D019384:Nucleic Acid Synthesis Inhibitors; D013439:Sulfhydryl Reagents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
D000970:Antineoplastic Agents; D002729:Chloromercuribenzoates; D004273:DNA, Neoplasm; D019384:Nucleic Acid Synthesis Inhibitors; D013439:Sulfhydryl Reagents; D004256:DNA Polymerase I; D004257:DNA Polymerase II; D005033:Ethylmaleimide; D004229:Dithiothreitol