PRESENCE OF IRON CATALYTIC FOR FREE-RADICAL REACTIONS IN PATIENTS UNDERGOING CHEMOTHERAPY - IMPLICATIONS FOR THERAPEUTIC MANAGEMENT

We investigated the kinetics of generation of iron 'catalytic' for fre e radical reactions in children with diagnosed acute lymphoblastic leu kaemia (ALL) who received high-dose methotrexate infusions. In 76% of the chemotherapy courses studied, 'catalytic' iron appeared in plasma in the concentration range from 0.1 to 3 mu mol/l. Positive correlatio ns between maximum levels of 'catalytic' iron and plasma hepatic enzym es could be established in the majority of cases and in one subset of patients (low and medium risk ALL) mean 'catalytic' iron levels correl ated well to clinically observable toxicities. The damaging potential of 'catalytic' iron was also demonstrated experimentally: oxidative da mage to proteins was significantly (P < 0.05) higher in plasma samples showing the presence of 'catalytic' iron and in addition a strong cor relation (r = 0.95, P < 0.02) was seen between plasma concentration of 'catalytic' iron and the ability of the plasma to stimulate lipid per oxidation. Our data show that chemotherapy releases 'catalytic' iron w hich may relate to toxic side effects. Hence binding this 'catalytic' iron by judicious co-administration of iron chelating agents could be beneficial in minimizing the iatrogenic adverse effects of chemotherap y of acute leukaemia.