Abstract
Cationic aromatic tricyclic compounds including triphenylmethane dyes, phenazines, phenoxazines, acridines, phenothiazines, phenanthridinium compounds, anthracenes and xanthene dyes, which amplify cell killing in phleomycin-treated Escherichia coli B cells also modified phleomycin-induced breakdown of DNA to acid-soluble fragments. A plot of DNA breakdown as a function of concentration was bell-shaped for each of the active compounds, i.e. as the concentration increased, DNA breakdown was enhanced initially, but above a certain concentration, the proportion of DNA degraded declined, often to zero. One of the compounds, acriflavine, when tested also inhibited DNA breakdown following ultraviolet irradiation. A study, by sedimentation methods, of DNA single-strand breakage in phleomycin-treated E. coli cells, using 3 representative compounds, Crystal Violet, 3,6-diaminoacridine and Methylene Blue, revealed a consistent increase in DNA strand breaks as concentration of compound increased. In similar experiments with ethidium bromide the breakage yield/concentration curve exhibited a maximum. In general, however, it seems that the inhibition of DNA-breakdown observed at higher concentrations of these amplifying compounds is not explicable by an effect on the primary breakage event, but is due to suppression of exonucleolytic activity in the cells.
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Selected References
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- BRADNER W. T., PINDELL M. H. Antitumour properties of phleomycin. Nature. 1962 Nov 17;196:682–683. doi: 10.1038/196682a0. [DOI] [PubMed] [Google Scholar]
- Eberhard C., Herrmann R. L. Effect of deoxyribonucleic acid ligands on deoxyribonucleases and deoxyribonucleic acid polymerase I of Escherichia coli K-12. J Bacteriol. 1972 Oct;112(1):224–230. doi: 10.1128/jb.112.1.224-230.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Farrell L., Reiter H. Phleomycin-stimulated degradation of deoxyribonucleic acid in Escherichia coli. Antimicrob Agents Chemother. 1973 Sep;4(3):320–326. doi: 10.1128/aac.4.3.320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grigg G. W. Amplification of phleomycin induced death and DNA breakdown by caffeine in Escherichia coli. Mol Gen Genet. 1970;107(2):162–172. doi: 10.1007/BF00333632. [DOI] [PubMed] [Google Scholar]
- Grigg G. W., Edwards M. J., Brown D. J. Effects of coumarin, thiopurines, and pyronin Y on amplification of phleomycin-induced death and deoxyribonucleic acid breakdown in Escherichia coli. J Bacteriol. 1971 Sep;107(3):599–609. doi: 10.1128/jb.107.3.599-609.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grigg G. W., Edwards M. J., Brown D. J. Effects of coumarin, thiopurines, and pyronin Y on amplification of phleomycin-induced death and deoxyribonucleic acid breakdown in Escherichia coli. J Bacteriol. 1971 Sep;107(3):599–609. doi: 10.1128/jb.107.3.599-609.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grigg G. W., Gero A. M., Hughes J. M., Sasse W. H., Bliese M., Hart N. K., Johansen O., Kissane P. Amplifications of phleomycin and bleomycin-induced antibiotic activity in Escherichia coli by aromatic cationic compounds. J Antibiot (Tokyo) 1977 Oct;30(10):870–878. doi: 10.7164/antibiotics.30.870. [DOI] [PubMed] [Google Scholar]
- Grigg G. W. Induction of DNA breakdown and death in Escherichia coli by phleomycin. Its association with dark-repair processes. Mol Gen Genet. 1969;104(1):1–11. doi: 10.1007/BF00277357. [DOI] [PubMed] [Google Scholar]
- Ishizuka M., Takayama H., Takeuchi T., Umezawa H. Studies on antitumor activity, antimicrobial activity and toxicity of phleomycin. J Antibiot (Tokyo) 1966 Nov;19(6):260–271. [PubMed] [Google Scholar]
- LERMAN L. S. Structural considerations in the interaction of DNA and acridines. J Mol Biol. 1961 Feb;3:18–30. doi: 10.1016/s0022-2836(61)80004-1. [DOI] [PubMed] [Google Scholar]
- McGrath R. A., Williams R. W. Reconstruction in vivo of irradiated Escherichia coli deoxyribonucleic acid; the rejoining of broken pieces. Nature. 1966 Oct 29;212(5061):534–535. doi: 10.1038/212534a0. [DOI] [PubMed] [Google Scholar]
- OKADA T., YANAGISAWA K., RYAN F. J. Elective production of thymine-less mutants. Nature. 1960 Oct 22;188:340–341. doi: 10.1038/188340a0. [DOI] [PubMed] [Google Scholar]
- ORGEL A., BRENNER S. Mutagenesis of bacteriophage T4 by acridines. J Mol Biol. 1961 Dec;3:762–768. doi: 10.1016/s0022-2836(61)80081-8. [DOI] [PubMed] [Google Scholar]
- Onishi T., Iwata H., Takagi Y. Effects of reducing and oxidizing agents on the action of bleomycin. J Biochem. 1975 Apr;77(4):745–752. doi: 10.1093/oxfordjournals.jbchem.a130778. [DOI] [PubMed] [Google Scholar]
- Stern R., Rose J. A., Friedman R. M. Phleomycin-induced cleavage of deoxyribonucleic acid. Biochemistry. 1974 Jan 15;13(2):307–312. doi: 10.1021/bi00699a012. [DOI] [PubMed] [Google Scholar]
- Veatch W., Okada S. Radiation-induced breaks of DNA in cultured mammalian cells. Biophys J. 1969 Mar;9(3):330–346. doi: 10.1016/S0006-3495(69)86390-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
