Mode of action illudin S.
The effect of the antitumor antibiotic illudin S on bacterial macromolecular synthesis was investigated. Illudin S was found to be inhibitory to in vivo deoxyribonucleic acid (DNA) synthesis from thymidine. Ribonucleic acid (RNA) synthesis was inhibited only at a concentration of illudin S 10 times that which inhibited DNA synthesis. The rate of protein synthesis remained the same except for a brief initial inhibition. When thymidine triphosphate was used for in vitro DNA synthesis, inhibition by illudin S did not occur, as tested with partially purified DNA polymerase II from Escherichia coli pol A(1) (-), with E. coli DNA-dependent RNA polymerase, with E. coli pol A(1) (-) spheroplasts, and with frozen and thawed Bacillus subtilis cells. A protein fraction isolated from B. subtilis capable of forming thymidine mono-, di-, and triphosphates from thymidine was not inhibited by illudin S. Furthermore, (14)C-illudin S taken up by B. subtilis cells was reisolated unchanged, making an intracellular activation of illudin S unlikely. Therefore, an attractive hypothesis is that illudin S inhibits DNA synthesis from thymidine which does not proceed through deoxyribonucleoside triphosphates, the generally accepted substrates for DNA synthesis.
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D004269:DNA, Bacterial / Q000096:biosynthesis*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D012329:RNA, Bacterial / Q000096:biosynthesis*; D012717:Sesquiterpenes / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D002250:Carbon Radioisotopes; D004269:DNA, Bacterial; D012329:RNA, Bacterial; D012717:Sesquiterpenes; D013141:Spiro Compounds; D014316:Tritium; D013936:Thymidine