Effects Of Quinacrine Research Articles

Quinacrine Skin Discoloration Is Associated with Fluorescence of `Y' Chromosome in Male Cells and Malarial Parasites in Malaria

Sokol et al reported yellow discoloration in a child treated with quinacrine for giardiasis. This, as the authors suggest, is a well known harmless side effect of quinacrine. During work with quinacrine fluorescence of the "Y" chromosome, we observed that malarial parasites within red cells of blood smears also fluoresced brightly. At that time we examined a smear of a Nigerian adult male with malaria, who had yellow discoloration due to quinacrine therapy. Not only did we demonstrate quinacrine fluorescence of "Y" chromosomes in white cells of his unstained blood smear but fluorescent malarial parasites were still present in some red cells.

End‐plate channel opening and the kinetics of quinacrine (mepacrine) block.

1. The effects of quinacrine on the relaxation of the agonist-induced currents in response to a voltage step were investigated at voltage clamped frog end-plates. A fast perfusion technique allowed the application of known concentrations of the agonist acetylcholine (ACh) or carbachol to end-plate viewed with Nomarski optics. 2. In the presence of quinacrine, and in response to a hyperpolarizing voltage jump, an agonist-induced current shows a fast initial relaxational increase and then relaxes slowly back to a new equilibrium level. 3. The slow relaxation can be described by a single exponential with a time constant tau s . tau s gets smaller at increasing quinacrine concentrations (0--2 microM) and the decay rate constant, 1/tau s, increases linearly with quinacrine concentration. Increasing agonist concentration reduces tau s, in a manner dependent on the nature of the agonist. Tau s is markedly lengthened at more hyperpolarized potential, but this voltage effect gets less at higher concentrations of agonist. 4. These data suggest a slow voltage dependent blockage of open end-plate channels by quinacrine. The binding rate constant of quinacrine is estimated as 10(8) M-1 s-1, and the voltage dependent, backward rate constant, as 5 s-1 at -60 mV and 1 s-1 at -140 mV. These values are in fair agreement with those obtained from the analysis presented in the preceding paper. 5. The agonist concentration dependence of the blocking kinetics is compatible with a simple model for channel opening. In this model, independent sequential binding of two agonist molecules leads to an isomerization of the receptor. The intrinsic binding constant of ACh is estimated to be around 20 microM, and for carbachol around 200 microM. Distinct isomerization constants could lead to a maximal activation of 70% of the available channels by ACh, and only 40% by carbachol. 6. An example of a possible interaction in between quinacrine block and desensitization is shown. At the break of an hyperpolarizing jump which has increased quinacrine blockade, a transient increase in the synaptic current is observed with apparently a temporary reduction of the desensitization.

Sensitivity of cells in exponential and stationary growth phase to combined treatment with radiation and quinacrine.

The effect of Quinacrine on the recovery of cells from sublethal radiation injury was analysed by testing cellular survival after exposure to low and high radiation doses, and after irradiation with split doses. Quinacrine was found to inhibit recovery in cell cultures in exponential growth phase but not, or only slightly, in cells in stationary growth. This finding is related to the inhibitory effect of Quinacrine on the repair of radiation induced DNA strand breaks.

GENETIC STUDIES OF ACRIDINE-INDUCED MUTANTS IN STREPTOCOCCUS PNEUMONIAE

The mutagenic properties of acridines on pneumococcus are described. All seven acridines tested were mutagenic at the amiA locus conferring a resistance to 10(-5) M aminopterin. The effects of quinacrine were more specifically investigated. It was observed that: mutants can be obtained only by treatment of exponentially growing cells; a sharp maximum mutagenic effect occurs at a concentration slightly lower than the bacteriostatic value; and the amount of quinacrine required to yield the maximum mutagenic effect decreases with the pH of the medium. Moreover, the number of mutants detected after quinacrine treatment varies from locus to locus. The majority of quinacrine-induced mutants are readily reverted by quinacrine, but not by nitrosoguanidine treatment. This suggests that in pneumococcus quinacrine induces mainly frameshift mutations. A further study of the revertants obtained by quinacrine treatment of quinacrine-induced mutants strengths this interpretation: most of the revertants result from a mutation at the same site; some partial revertants exhibiting an intermediate resistance to aminopterin were found to contain two very closely linked mutated sites, each mutation conferring the maximum level of resistance to aminopterin. Thus, the majority of quinacrine-induced mutants at the amiA locus of pneumococcus consists of frameshift mutations. Nearly all of the isolated mutants induced by quinacrine as well as other acridines belong to the low efficiency class of transformation. It was concluded that the mismatch resulting from the pairing between the wild type and the frameshift-containing sequence is recognized by the excision-repair system involved in the discrimination function in a way similar to that in which it recognizes mismatched base pairs between a transition mutation and the wild-type sequence.

Third annual David A. Karnofsky Memorial Lecture. The compleat clinical oncologist: a new approach to training.

Third annual David A. Karnofsky Memorial Lecture. The compleat clinical oncologist: a new approach to training.

Effect of Quinacrine on X-Ray Sensitivity and the Repair of Damaged DNA in Escherichia coli K-12

Quinacrine (0.15 mM), when added to the postirradiation incubation medium of E. coli K-12 rec+ cells, markedly potentiated the killing induced by x-irradiation. Alkaline sucrose gradient studies showed that quinacrine was a potent inhibitor of the repair of DNA single-chain breaks in rec+ cells and that this inhibition was largely irreversible. The recA13 mutant (deficient in the slow repair of x-ray induced single-chain breaks in DNA) did not show radiation sensitization by quinacrine. The possible use of quinacrine as a radiation potentiator in humans is discussed.

Effect of Quinacrine on Neoplastic Effusion and Certain of Their Enzymes

Effect of Quinacrine on Neoplastic Effusion and Certain of Their Enzymes

The effect of quinacrine on neoplastic effusions and certain of their enzymes.

The effect of quinacrine on neoplastic effusions and certain of their enzymes.

Quinacrine (atabrine) in treatment of solar dermatoses.

During the past year we have had excellent results in treating chronic discoid lupus erythematosus with quinacrine (Atabrine) hydrochloride. As the great number of solar dermatoses begin each spring we had planned to see what effect the drug would have in these cases, since Page 1 had shown the time necessary to produce a minimum erythema dose of ultraviolet light to be increased from 6 to 24 seconds in one patient receiving quinacrine for 10 days; another patient receiving the drug for a similar time had shown an increase from 20 to 36 seconds. Page 1 felt that much of the effect of quinacrine in lupus erythematosus was due to the pigmentation of the skin decreasing the photosensitive reaction, which is recognized as a potent factor in this disease. He did note that this pigmentation did not explain the beneficial effects in systemic manifestations of the disease. Sulzberger and

The effects of quinacrine (atabrine) suppression on the course of pacific vivax malaria

The effects of quinacrine (atabrine) suppression on the course of pacific vivax malaria