HEMOZOIN PRODUCTION BY PLASMODIUM-FALCIPARUM - VARIATION WITH STRAIN AND EXPOSURE TO CHLOROQUINE

Synchronized Plasmodium falciparum parasites were grown in erythrocyti c culture for measurement of malaria pigment (hemozoin) production usi ng a simple method based on the insolubility of beta-hematin, the prin cipal pigment of hemozoin. In the last 44 h of the life cycle, one str ain (chloroquine-susceptible) incorporated an average of 960 pmol of f erriprotoporphyrin IX (FP) from hemoglobin into beta-hematin per 10(6) parasitized erythrocytes. By comparison, another strain (chloroquine- resistant) incorporated 515 pmol of FP into beta-hematin. When exposed to 25 ng of chloroquine per ml of culture medium, chloroquine-suscept ible P. falciparum incorporated 240 pmol of FP into beta-hematin per 1 0(6) parasitized erythrocytes in one intraerythrocytic life cycle. In contrast chloroquine-resistant P. falciparum exposed to 100 ng of chlo roquine per ml incorporated 630 pmol of FP into beta-hematin. Thus, ch loroquine inhibits hemozoin production in chloroquine-susceptible P. f alciparum but not in chloroquine-resistant P. falciparum. On the contr ary, sublethal concentrations of chloroquine partially reverse a defic iency of hemozoin production in chloroquine-resistant P. falciparum. T hese results indicate that the adaptation responsible for chloroquine resistance in P. falciparum prevents the accumulation of toxic FP by p reventing chloroquine from uncoupling the processes of hemoglobin degr adation and hemozoin production.