PT - JOURNAL ARTICLE AU - JOHN FOK AU - MICHAEL WARING TI - Breakdown of Pulse-Labeled Ribonucleic Acid in <em>Bacillus megaterium</em>, Revealed by Exposure to the Antibiotics Mithramycin, Chromomycin, and Nogalamycin DP - 1972 Jan 01 TA - Molecular Pharmacology PG - 65--74 VI - 8 IP - 1 4099 - http://molpharm.aspetjournals.org/content/8/1/65.short 4100 - http://molpharm.aspetjournals.org/content/8/1/65.full SO - Mol Pharmacol1972 Jan 01; 8 AB - The decay of pulse-labeled RNA in Bacillus megaterium in the presence of actinomycin D, mithramycin, chromomycin A3 , nogalamycin, and daunomycin was investigated. Actinomycin (10 µg/ml) was found to induce decay characterized by a half-life (t1/2) of 50 ± 1.4 sec and a stable fraction of 45 ± 1.0% (eight determinations), comparable with estimates obtained by other workers. Concentrations of mithramycin between 5 and 1OO µ/ml were found to induce decay. The values of t1/2 and the stable fraction decreased with increasing mithramycin concentration, approaching values similar to those found with actinomycin. Chromomycin at concentrations between 2 and 50 µg/ml produced decay, and at intermediate concentrations the t1/2 and stable fraction approximated the values given by actinomycin. Nogalamycin at concentrations in the range 8-50 µg/ml induced decay characterized by t1/2 values significantly higher than those found with actinomycin, though values of the stable fraction at concentrations up to 20 µg/ml were essentially the same as seen with actinomycin. RNA synthesis was inhibited by daunomycin at concentrations up to 80 µg/ml, revealing slight decays, but at 160 µg/ml inhibition of RNA synthesis without perceptible decay was observed. It is concluded that the parameters of decay induced by mithramycin and chromomycin corroborate those observed with actinomycin, but that nogalamycin yields significantly different results and that daunomycin is not a suitable antibiotic for studying decay of pulse-labeled RNA. Possible explanations for the failure of nogalamycin and daunomycin to induce actinomycin-like decay, such as slow penetration of the antibiotics into the cells, binding to RNA, or direct interference with protein synthesis, are discussed. ACKNOWLEDGMENTS The participation of C. A. Stubbings during preliminary stages of this work is acknowledged. We thank Drs. E. Cundliffe and J. Grinsted for advice and encouragement.