Abstract |
Formycin B inhibited growth of L5178Y mouse leukemia cells in concentrations of less than twice the concentration that inhibits cell proliferation at 50% by cytostasis; at higher concentrations (more than twice the 50% concentration mentioned), the cells were killed. In cells treated with the concentration that inhibits cell proliferation at 50%, the average cell volume did not change. The formycin B inhibitory effect on cell proliferation was reduced by coincubation with nicotinamide adenine diphosphate or adenosine. The biosyntheses of DNA, RNA, and protein in whole cells were sensitively inhibited by formycin B as checked by incorporation studies with radioactive precursors. In addition, the formation of polyadenosine diphosphoribose was reduced even with higher sensitivity; in particular the extent of adenosine diphosphate ribosylation of histone subfraction H1 was reduced. Formycin B has been shown to be an inhibitor for the polyadenosine diphosphoribose polymerase, isolated from oviduct nuclei of quails. Both the chromatin-bound and the soluble enzyme are inhibited competitively; the relative affinity (Ki/Km) of formycin B to the polyadenosine diphosphoribose polymerase is 1.5.
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Authors | W E Müller, H J Rohde, R Steffen, A Maidhof, M Lachmann, R K Zahn, H Umezawa |
Journal | Cancer research
(Cancer Res)
Vol. 35
Issue 12
Pg. 3673-81
(Dec 1975)
ISSN: 0008-5472 [Print] United States |
PMID | 172231
(Publication Type: Journal Article)
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Chemical References |
- Antibiotics, Antineoplastic
- Chromatin
- DNA, Neoplasm
- Formycins
- Histones
- Neoplasm Proteins
- Nucleoside Diphosphate Sugars
- RNA, Neoplasm
- NAD
- Poly Adenosine Diphosphate Ribose
- NAD+ Nucleosidase
- Adenosine
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Topics |
- Adenosine
(pharmacology)
- Animals
- Antibiotics, Antineoplastic
(pharmacology)
- Cell Division
(drug effects)
- Cell Survival
(drug effects)
- Cells, Cultured
- Chromatin
(metabolism)
- DNA, Neoplasm
(biosynthesis)
- Dose-Response Relationship, Drug
- Formycins
(pharmacology)
- Histones
(metabolism)
- Leukemia, Experimental
(metabolism)
- Mice
- NAD
(pharmacology)
- NAD+ Nucleosidase
(metabolism)
- Neoplasm Proteins
(biosynthesis)
- Nucleoside Diphosphate Sugars
(biosynthesis)
- Poly Adenosine Diphosphate Ribose
(biosynthesis)
- RNA, Neoplasm
(biosynthesis)
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