ABSTRACT
This comparative study was made to examine chroloquine inhibition of C14-hypoxanthine incorporation (preferably nucleic acid precursor for plasmodium) in the short-living red blood cell cultures in mice infected with P. berghei strains differently sensitive to the agent 24 hours after incubation. These included 1) chloroquine-sensitive H strain; 2) LNK-65 strain having a spontaneously 2-3-fold decreased sensitivity to the agent; 3) strain LNK-65 ChR selected for high resistance to chloroquine. IC50 (chloroquine concentrations that ensure 50% inhibition of the incorporation of nucleic acid precursor into the cells of the parasite) was estimated for 3 P. berghei strains that were differently sensitive to chloroquine. These in vitro values adequately reflect the sensitivity of these strains to the agent in vivo.
Subject(s)
Antimalarials/pharmacology , Chloroquine/pharmacology , Erythrocytes/parasitology , Plasmodium berghei/drug effects , Animals , Cells, Cultured , Drug Evaluation, Preclinical/methods , Drug Resistance , Longevity , Mice , Plasmodium berghei/isolation & purificationSubject(s)
Antimalarials/pharmacology , Chloroquine/pharmacology , DNA, Protozoan/drug effects , Plasmodium berghei/drug effects , Plasmodium berghei/genetics , RNA, Protozoan/drug effects , Animals , Cytochrome P-450 Enzyme System/genetics , DNA, Complementary , Drug Resistance/genetics , Gene Expression Regulation, EnzymologicABSTRACT
A comparative restriction analysis was made for DNA in malaria parasites, strain H sensitive to chloroquinone, strain LNK-65 with spontaneously occurred resistance to the agent, and breeding strain LNK-65 ChlR highly resistant to it. DNA hydrolysis with EcoR1, HindIII, and BamH1 endonucleases revealed permanent differences in the DNA restriction pattern of malaria parasites. There were additional restriction bands as part of DNA restricts in the strain LNK-65 Chl bred from LNK-65 for high resistance to chloroquine on EcoR1-, HindIII-, and BamH1-hydrolysis. Great differences in the DNA restriction pattern in the strains H and LNK-65 are likely to be due to their belonging to various strains, such as P.berghei and P.yoelii, respectively. Comparison of the DNA restriction pattern of the host (murine leukocytes) and the malaria parasite suggests the plasmodium DNA is adequately removed from the host DNA.
