Influence of formycin B on polyadenosine diphosphoribose synthesis in vitro and in vivo.
Cancer Res, 1975/12;35(12):3673-81.
Müller WE, Rohde HJ, Steffen R, Maidhof A, Lachmann M, Zahn RK, Umezawa H
PMID: 172231
Impact factor: 13.312
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.
MeSH terms
Adenosine; Animals; Antibiotics, Antineoplastic; Cell Division; Cell Survival; Cells, Cultured; Chromatin; DNA, Neoplasm; Dose-Response Relationship, Drug; Formycins; Histones; Leukemia, Experimental; Mice; NAD; NAD+ Nucleosidase; Neoplasm Proteins; Nucleoside Diphosphate Sugars; Poly Adenosine Diphosphate Ribose; RNA, Neoplasm
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