608 TIME SEQUENCE OF RBC PROTOPORPHYRIN (PP) ACCUMULATION IN LEAD POISONING

Abstract

Lead intoxication in children deranges the last step in heme synthesis and results in the accumulation in the RBCs of protoporphyrin in the form of the Zn-chelate (ZnPP); some patients however exhibit an increased level of unchelated PP (Free PP). To evaluate the hypothesis that Free PP accumulates first and is later converted to ZnPP, the sequence of accumulation of the two PP types was followed in lead poisoned animals. Total PP, ZnPP, and Free PP were quantitated by fluorescence spectrophotometry. Three different species were used:rats, guinea pigs and rabbits. In rats and guinea pigs, increase in total PP was prompt (within 10 days) but modest (3× normal); in rabbits the increase in total PP was more marked (10× normal). Initially in all 3 species there was a rapid increase in Free PP, with a subsequent increase in ZnPP. During Pb intoxication, the relative concentration of the two types of PP was measured in RBCs separated according to age on density gradients. There was 4 times more Free PP than ZnPP in the youngest RBCs, while the oldest RBCs contained 3 times more ZnPP than Free PP. After Pb administration was discontinued the predominant PP species was ZnPP and the concentration of Free PP was minimal. These data indicate that the effect of Pb on heme synthesis results in initial accumulation of Free PP which later chelates Zn to form ZnPP. Extrapolation of these data to humans suggests that when in children both Free PP and ZnPP are present, the exposure to lead is recent.