Plasmodium falciparum: chloroquine selection of a cloned line and DNA rearrangements.
The chloroquine-sensitive Plasmodium falciparum clone, HB3, was selected for growth in increasing amounts of chloroquine. Increases in the size of chromosome 3 were observed with increased chloroquine selection, with the less chloroquine-sensitive parasites possessing the larger forms of the chromosome. Removal of chloroquine selection resulted in a decrease in size of the larger form to the original size and reexposure of these parasites to chloroquine selected again for parasites with a larger chromosome 3. These results suggest that the increase in size of chromosome 3 was associated with the decreased drug sensitivity in the chloroquine selected parasites. A macrorestriction map of chromosome 3 was constructed using the parent HB3 and drug selected lines. The chromosomal size increase was found to have resulted from DNA amplification occurring in 100-kb amplicons. Other isolates of P. falciparum were screened for large size polymorphism in chromosome 3 to determine if chromosome amplification events in this area of the genome also occurred in field isolates. No size changes that correlated with the amplified region in the chloroquine selected lines were observed.
Lim
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AS
Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Cowman
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AF
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D016054:DNA, Protozoan / Q000032:analysis / Q000737:chemistry / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005784:Gene Amplification / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D008970:Molecular Weight; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics; D015183:Restriction Mapping
D018528:ATP-Binding Cassette Transporters; D000962:Antimalarials; D016054:DNA, Protozoan; D015800:Protozoan Proteins; C059987:mdr gene protein, Plasmodium; D002738:Chloroquine; D012319:RNA Polymerase II