A. VANNOTTI 



Ph eny/hy drazin e 



We should like to present briefly here our researches which led to 

 the conclusion that lead inhibits the synthesis of haemoglobin. We 

 studied in man and in rabbit the metabolism of iron in lead poisoning, 

 making use especially of non-haemoglobin iron in the serum and 

 later of radioactive iron. We often found that the percentage of 

 non-haemoglobin iron increased during lead poisoning and the fact 

 that phenylhydrazine produced increased haemolysis showed clearly 

 that the increase of non-haemoglobin iron was more marked and of 

 longer duration than in the normal animal (rabbit. See Figure 1). 

 The increase of iron after haemolysis can be explained either by an 

 insufficient storage of iron in the spleen during the poisoning, or by 

 the inability of the bone marrow in lead-poisoned animals to make 

 use of iron. However we were able to eliminate the first possibility 

 by comparing the results of haemolysis due to lead poisoning in normal 

 animals with those in splenectomized animals 14 . 



In this connection it is 

 interesting to note that if 

 we carry out a splenectomy 

 and a very strong blockade 

 of the reticuloendothelial 

 system, and if we then in- 

 duce lead poisoning, anaemia 

 rapidly appears but is not ac- 

 companied by an increased 

 production of protopor- 

 phyrin. The disturbances 

 Figure 1 of the metabolism of non- 



haemoglobin iron were also pointed out by J. E. Kench, A. E. Gillam 

 and R. E. Lane 8 who, like ourselves, found increased values of iron 

 in the bloodstream. Finally, by means of radioactive iron, we were 

 able to observe in lead poisoning, after intravenous injection of radio- 

 active iron lactate, a notable increase of iron in the serum, a more 

 rapid and considerable storage of iron in the liver than in the normal 

 subject, and a significant accumulation of iron in the bone marrow 

 (see Figure 2). These experiments confirm the hypothesis that lead 

 does not interfere with the passage of the iron through the storage 

 organs, but that it merely inhibits the utilization of iron for the 

 synthesis of haemoglobin in the bone marrow. 



Examination by fluorescence microscopy shows that in lead poison- 

 ing the bone marrow and especially the erythroblasts are most rich in 

 porphyrin. By separating by means of centrifugation (according to 

 the method of Claude) the cells of the reticulum, the nuclei of the 

 cells in the bone marrow, and their cytoplasm, we were able to observe 



y Erythrocytes 



Fe y% 



Erythrocytes. 

 Fe y% 



254 



