654 ADVENTURES IN RADIOISOTOPE RESEARCH 



Comment on papers 61 — 65 



The method of in vitro labelling of plasma by adding minute amounts of iron 

 of high specific activity worked out in the Donner Laboratory by Huff et al. 

 (1950) proved to be most useful and found a very extended apphcation. In paper 

 61 by making use of this device, the effect of adrenahn on the rate of extrusion 

 of 5^Fe from the plasma was investigated. The marked increase of extrusion rate 

 observed can hardly be due to the effect of adrenahn on the permeabihty of the 

 capillary wall, since extrusion of ^^Na from the plasma was not found to be accele- 

 rated after injection of adrenalin. It is due to an increased rate of uptake of 

 s^Fe by the tissue cells. 



Even when exposing a rabbit to a heavy dose of 1500 r, 1 hr after exposure 

 the rate of extrusion of ^^Fe from the plasma, which is mainly due to a transport 

 to the bone marrow, is not much reduced. If we wait for 48 hr after exposure, 

 the effect of 800 r is found to be more effective in reducing the exodus of ^^Fe 

 from the plasma than are 1500 r after the lapse of 1 hr. Hennessy and Huff 

 (1950) have already previously shown that the optimal depression of ^^Fe incor- 

 poration into erythrocytes is obtained 1 to 2 days after exposure. This result, 

 and the observations stated in paper 61 suggested the explanation that it is not 

 the haemoglobin synthesis which is radiosensitive, but the blocking of haemoglo- 

 bin formation under the effect of irradiation is due to interference with cell divi- 

 sion and to cell destruction. The correctness of this view was brought out by the 

 autographic investigations of Lajtha et al. (1955). In following up cellular pro- 

 cesses the autographic technique proved to be a most powerful line of approach. 



As described in paper 62 the nuclear fraction of the rat and rabbit liver contains 

 a small amount of haemoglobin non-extractable in aqueous medium. The incorpo- 

 ration of ^*Fe into this fraction was also found to be radiosensitive, not however 

 its incorporation into ferritin or cytochrome b. Due to the blocking of incor- 

 poration of^^Fe into haemoglobin under the effect of irradiation, the specific acti- 

 vity of ferritin, ferrosiderin and other iron compounds of the hver increases. 

 Quite recently Theorell and Akeson succeeded in preparing highly pure myo- 

 globin. By availing ourselves of this method when isolating myoglobin from rat 

 muscles we found the hemin moiety of myoglobin to be radiosensitive only. 



Since the availabihty of the scintillation counter the activity of blood and 

 other labelled iron containing samples is mostly measured by making use of this 

 apparatus. Prior to the availability of the latter we precipitated the iron after 

 wet combustion of the sample as sulphide and measured the activity of the preci- 

 pitate with the Geiger counter as described in paper 65. Minute activities are 

 still preferably measured by making use of the last-mentioned procedure. 



References 



R. L. Huff, T. G. Hennessy, R. E. Austin, J. F. Garcia, B. M. Roberts and 



J. H. Lawrence (1950) J. Clin. Inv. 29, 1041. 

 T. G. Hennessy and R. L. Huff (1950). Proc. Soc. Biol. Med. 73, 436. 

 K. Agner, R. Bonnichsen and G. Hevesy (1954) J. Lab. Clin. Inv. 6, 261. 

 L. G. Lajtha and H. D. Suit (1955) Brit. J . Haematolog. 1, 55. 



