Reactions of quinine, chloroquine, and quinacrine with DNA and their effects on the DNA and RNA polymerase reactions.

O’Brien, Richard L.; Olenick, John G.; Hahn, Fred E.

doi:10.1073/pnas.55.6.1511

Cited by 136 publications

(62 citation statements)

References 24 publications

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“…A bactericidal concentration prevented DNA synthesis entirely, whereas protein and RNA synthesis continued though at a considerably reduced rate. This selective effect on DNA synthesis of E. coli by quinacrine was related to the greater sensitivity of DNA polymerase than RNA polymerase to quinacrine (O'Brien et al 1966). Thus, in B. cereus it is unlikely that growth inhibition by quinacrine is due to failure of DNA strand separation and cessation of DNA formation.…”

Section: L Seligman a N D H G M A N D E Lmentioning

confidence: 82%

“…The detailed mechanism of the selective block of RNA formation in Bacillus cereus may be due to inhibition of RNA polymerase by quinacrine, as reported for Escherichia coli (O'Brien et al 1966). Since the effect was more pronounced on ribosomes or rRNA formation than on sRNA, it is also possible that quinacrine produced a 'shift-down' effect.…”

Section: L Seligman a N D H G M A N D E Lmentioning

confidence: 83%

“…6). Whether this effect is due to the known stimulation of RNApolymerase by spermine (Krakow, 1963;O'Brien et al 1966), the amine's ability to displace quinacrine from DNA or the compound's capacity to stabilize ribosomes (Colbourn, Witherspoon & Herbst, 1961 ;Hershko, Amoz & Mager, 1961) is still unclear.…”

Section: Discussionmentioning

confidence: 99%

“…It is generally assumed that the antimalarial drug, quinacrine, owes its growth-inhibitory properties to a complexing with DNA (Irvin & Irvin, 1954;Kurnick & Radcliffe, 1962;Lerman, 1963 ;O'Brien, Olenick & Hahn, 1966) which leads to the failure of strand separation and the cessation of DNA synthesis (Ciak & Hahn, 1967). It therefore became of interest to examine the actions of the drug in a microbial system, Bacillus cereus, in which DNA synthesis continued while growth was completely inhibited (Mandel & Seligman, 1966.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Growth and RNA Biosynthesis of Bacillus cereus by Quinacrine

Seligman

Mandel

1971

Journal of General Microbiology

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SUMMARYThe addition of 0.4 mmquinacrine to exponential cultures of Bacillus cereus led to the complete inhibition of growth, measured turbidimetrically. Certain metal ions such as Ca2+ and Mg2+ were partially effective in preventing growth inhibition, as was the polyamine spermine.Quinacrine inhibited most biosynthetic processes measured to the same extent as the reduction in the rate of growth. Thus the incorporation of amino acids into protein, that of diaminopimelic acid into bacterial wall, the accumulation of Kf and the uptake of nicotinic acid were diminished only in accordance with the decreased rate of turbidimetric increase. DNA biosynthesis was decreased to a lesser extent than was turbidity and continued even after growth had ceased altogether, thus indicating less inhibition of this process than that of protein formation. RNA synthesis, on the other hand, was selectively inhibited in these cells. The depressant effect was most pronounced when ribosomal or rRNA formation was examined. RNA isolated from drug-treated cells still exhibited messenger function. An additional effect of quinacrine on the uptake of certain nucleic acid bases is also postulated. The relative content of ATP in the cells was considerably increased by drug treatment.It appears that quinacrine did not exert its major action on DNA biosynthesis but selectively blocked RNA formation while that of DNA was permitted to continue.

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Section: L Seligman a N D H G M A N D E Lmentioning

confidence: 82%

Section: L Seligman a N D H G M A N D E Lmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Growth and RNA Biosynthesis of Bacillus cereus by Quinacrine

Seligman

Mandel

1971

Journal of General Microbiology

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“…We have recently reported circumstantial evidence which suggests that DNA is the cellular target for these diverse inducers (16,(20)(21)(22)38). The DNA binding (32) of certain pisatin inducers such as quinacrine (20) and ethidium bromide can be discerned (8,9) at the chromosome level in peas as fluorescing bands or mosaics which are chromosome-and species-specific.…”

Section: Discussionmentioning

confidence: 99%

Mode of Pisatin Induction

Hadwiger¹,

Jafri²,

Broembsen³

et al. 1974

Plant Physiol.

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Increases in phenylalanine ammonia lyase activity and pisatin synthesis were induced in excised pea pods (a) by basic polypeptides such as protamine, histone, lysozyme, cytochrome c, and ribonuclease; (b) by the polyamines spermine, spermidine, cadaverine, and putrescine, and (c) by the synthetic oligopeptides poly-L-lysine, poly-DL-ornithine, and poly-Poly-L-lysine (1 milligram per milliliter, molecular weight 7,200) was utilized as a model inducer of pisatin and phenylalanine ammonia lyase. The poly-L-lysine-induced responses could be inhibited by adding the RNA synthesis inhibitors cordycepin or a-amanitin to the pods prior to or at the time of inducer application. Cordycepin added 1.5 hours after inducer no longer completely inhibited induction. The application of poly-L-lysine was shown to characteristically change the rate of RNA synthesis within 30 minutes. Ultrastructural changes in pea nuclei were detected within 3 hours, and gross changes in nuclear morphology were apparent at 14 hours after inducer application. The physical appearance of uranyl acetate-stained chromatin isolated from poly-L-lysine 2 hours after inducer application differed from that of water-treated tissues. The template properties of chromatin extracted from pods 3 hours after inducer application were consistently superior to control chromatin when assayed with Escherichia coli RNA polymerase (without sigma factor). Chromatin from poly-L-lysine-induced tissue also bound 49% more actinomycin D-'H.The DNA-complexing properties of inducer compounds and the induced changes in the template and dye-binding properties of pea chromatin formed the basis for a proposed mode of action for phytoalexin induction.The functions of numerous polypeptide hormones (5) have been characterized in animal systems; however, interest in the potential role of polypeptides in regulating plant processes is still limited. There is reason to believe that numerous polypeptide components remain to be discovered which can influence plant cell processes (46). Phytoalexin induction in pea tissue has been employed as one measure of the effects of chemically defined compounds on the regulation of cell processes (12,(15)(16)(17)(18)(19)(20)(21)38). We now report that basic peptides can induce gene-controlled responses, and we demonstrate that this gene-activating potential exists for basic compounds (2, 41, 47) which occur in plants and other higher organisms.The synthetic compound, poly-L-lysine, was chosen as a model inducer because of its amino acid residue uniformity and chemical simplicity. This paper examines the phytoalexininducing effect of poly-L-lysine in relation to (a) alteration of the fine structure of nuclei and cell membranes, (b) template activity and dye-binding capacity of isolated chromatin, (c) the in vivo rate of RNA synthesis, and (d) the dependency of the induction process on RNA and protein synthesis.Our previous hypothesis (20, 38) that regulation of gene expression can occur as a result of changes in the conformation of specific segment...

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