Oncology
Original Paper
Growth Inhibitory Activity of Succinylacetone: Studies with Walker 256 Carcinosarcoma, Novikoff Hepatoma and L1210 LeukemiaTschudy D.P.a · Ebert P.S.b · Hess R.A.a · Frykholm B.C.a · Atsmon A.caMetabolism Branch and bLaboratory of Molecular Oncology, National Cancer Institute, Bethesda, Md., USA; cBeilinson Hospital, Petah Tikva, Israel
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Article / Publication Details
Published online: June 11, 2009
Issue release date: 1983
Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 0
ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)
For additional information: https://www.karger.com/OCL
Abstract
Succinylacetone (SA, 4,6-dioxoheptanoic acid) inhibits d-aminolevulinic acid dehydrase, the second enzyme of the heme biosynthetic pathway and thereby inhibits heme biosynthesis. In the present study SA is shown to inhibit the growth of the Walker carcinosarcoma (W256) in vitro and in vivo, the Novikoff hepatoma in vivo, and L1210 leukemia in vitro, but only slightly in vivo. Rats can tolerate significantly larger doses of SA for at least twice as long as were administered in the present study without gross evidence of toxicity. In contrast to findings in previously published studies with murine erythroleukemia cells, the inhibition of growth of L1210 and W256 cells by SA in vitro is not accompanied by a decrease in cellular heme and is not reversed by addition of hematin to the medium. This suggests a second mechanism of growth inhibition of tumor cells unrelated to heme biosynthesis. Although the growth of both W256 and L1210 cells was markedly inhibited by the same concentration of SA in culture, there was a great difference in responsiveness in vivo, in that much greater inhibition of the growth of the Walker tumor was produced by SA.
© 1983 S. Karger AG, Basel
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Article / Publication Details
Published online: June 11, 2009
Issue release date: 1983
Number of Print Pages: 7
Number of Figures: 0
Number of Tables: 0
ISSN: 0030-2414 (Print)
eISSN: 1423-0232 (Online)
For additional information: https://www.karger.com/OCL
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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