Induction of gene amplification in Plasmodium falciparum
Human erythrocytic in vitro cultures of Honduras I strain of the malaria parasite Plasmodium falciparum have been stressed stepwise with increasing concentrations of methotrexate (MTX), a folate antagonist. This selection has produced a strain that is 450 times more resistant to the drug than the original culture. Uptake of sublethal doses of radiolabeled MTX by infected red blood cells was 6-36 times greater in the resistant cultures than in the nonresistant controls. DNA isolated from all of the parasites was probed by hybridization with /sup 35/S-labeled DNA derived from a clone of the yeast thymidylate synthetase (TS) gene. This showed 50 to 100 times more increased hybridization of the TS probe to the DNA from the resistant parasites is direct evidence of gene amplification because DHFR and TS are actually one and the same bifunctional enzyme in P. falciparum. Hence, the evidence presented indicates that induced resistance of the malaria parasite to MTX in this case is due to overproduction of DHFR resulting from amplification of the DHFR-TS gene.
- Research Organization:
- American Univ., Washington, DC
- OSTI ID:
- 7246176
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTIMETABOLITES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MATERIALS
BIOLOGY
BLOOD
BLOOD CELLS
BODY FLUIDS
DAYS LIVING RADIOISOTOPES
DISEASE RESISTANCE
DNA
DRUGS
ENZYMES
ERYTHROCYTES
EVEN-ODD NUCLEI
GENES
GENETICS
HYBRIDIZATION
IN VITRO
INVERTEBRATES
ISOTOPE APPLICATIONS
ISOTOPES
LIGASES
LIGHT NUCLEI
MAMMALS
MAN
MATERIALS
METHOTREXATE
MICROORGANISMS
NUCLEI
NUCLEIC ACIDS
ORGANIC COMPOUNDS
PARASITES
PLASMODIUM
PRIMATES
PROTOZOA
RADIOISOTOPES
SPOROZOA
SULFUR 35
SULFUR ISOTOPES
TRACER TECHNIQUES
VERTEBRATES