Document Detail

Inhibition of bleomycin-induced [3H] thymidine 5'-triphosphate incorporation into liver and hepatoma nuclei by N-ethyl maleimide and daunomycin.
MedLine Citation:
PMID:  66227     Owner:  NLM     Status:  MEDLINE    
The addition of bleomycin to a nuclear incorporating system results in an increased incorporation of 3H-thymidine 5'-triphosphate (3H-TTP) into the DNA of liver and hepatoma nuclei. Bleomycin added to the nuclear incorporating system also produces scissions of DNA as determined by sucrose density gradient centrifugation of the extracted DNA. The action of bleomycin is dependent on the presence of sulfhydryl agents in the incubation mixture. Two compounds, N-ethyl maleimide and daunomycin, inhibit the bleomycin-induced incorporation of 3H-TTP preferentially. N-Ethyl maleimide inhibits bleomycin-induced activity in liver and hepatoma 7777 nuclei equally. Lower levels of daunomycin inhibit the bleomycin-induced activity in the hepatoma 7777 nuclei than are required to inhibit the activity in liver nuclei. The two compounds inhibit the bleomycin effect by different mechanisms. The addition of N-ethyl maleimide to bleomycin in the incubation system prevents bleomycin from causing breaks in the DNA. The addition of daunomycin, despite inhibition of bleomycin-induced 3H-TTP incorporation, does not affect the bleomycin-produced breaks in the DNA. N-Ethyl maleimide acts by binding to the DNA and by competing with a sulfhydryl agent for bleomycin-sensitive sites on the DNA. Daunomycin apparently inhibits a repair enzyme that is responsible for the increased incorporation following bleomycin treatment.
M L Coetzee; G P Sartiano; K Klein; P Ove
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  The Journal of antibiotics     Volume:  30     ISSN:  0021-8820     ISO Abbreviation:  J. Antibiot.     Publication Date:  1977 Feb 
Date Detail:
Created Date:  1977-05-27     Completed Date:  1977-05-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0151115     Medline TA:  J Antibiot (Tokyo)     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  163-71     Citation Subset:  IM    
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MeSH Terms
Binding Sites
Binding, Competitive
Bleomycin / antagonists & inhibitors*,  pharmacology
Carcinoma, Hepatocellular / metabolism*
Cell Nucleus / metabolism*
DNA / biosynthesis
Daunorubicin / pharmacology*
Liver / metabolism*
Liver Neoplasms / metabolism*
Maleimides / pharmacology*
Thymine Nucleotides / metabolism*
Reg. No./Substance:
0/Maleimides; 0/Thymine Nucleotides; 11056-06-7/Bleomycin; 20830-81-3/Daunorubicin; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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