Influence of formycin B on polyadenosine diphosphoribose synthesis in vitro and in vivo.
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.
D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005573:Formycins / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D009243:NAD / Q000494:pharmacology; D009244:NAD+ Nucleosidase / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis; D009702:Nucleoside Diphosphate Sugars / Q000096:biosynthesis*; D011064:Poly Adenosine Diphosphate Ribose / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis
D000903:Antibiotics, Antineoplastic; D002843:Chromatin; D004273:DNA, Neoplasm; D005573:Formycins; D006657:Histones; D009363:Neoplasm Proteins; D009702:Nucleoside Diphosphate Sugars; D012334:RNA, Neoplasm; D009243:NAD; D011064:Poly Adenosine Diphosphate Ribose; D009244:NAD+ Nucleosidase; D000241:Adenosine