J. M. GARVAN, E. P. GEORGE, F. A. ROCKE, AND S. VINCE 



source of irradiation in preference to ^^P for the following reasons. Firstly, 

 presumably the selective incorporation of the colloid into the recticulo- 

 endothelial elements of the bone marrow should, in view of the short range 

 of the principal ionizing component of radiation emitted by ^^*Au, give 

 maximum discrimination in favour of irradiation of marrow rather than 

 bone. Secondly, subsequent transfusion of bone marrow with minimum 

 damage to the transfusion from residual radio-activity can be made earlier in 

 the case of ^^^Au because of its shorter physical half-life, 2 • 7 days as against 

 14 days for ^^P. And thirdly, problems of radiometric assay of specimens 

 are simplified in the case of ^^^Au because of the emitted y radiation. 



We accordingly decided to investigate the possible role of ^^®Au in the 

 destruction of the bone marrow in the rabbit. 



If this could be achieved we proposed to follow this up with bone-marrow 

 transfusions in animals receiving this form of irradiation. 



The results of this investigation are described in the following paper. 



METHOD 



Except for the first series, adult rabbits, hutch-bred and without regard to 

 strain or sex, were used. 



The colloidal ^^^Au* was administered via the ear vein, being diluted if 

 necessary with physiological saline. The Amersham catalogue states that 

 the colloid as supplied contains some glucose and about 0-05m sodium 

 chloride, and is stabilized with gelatin. The gold concentration was 

 10 mg/ml. Those rabbits which received the dose on which we finally 

 settled, each received of the order of 5 mg of gold. This should be well below 

 the minimum toxic level. The best information that we have to date re- 

 garding particle size is that most particles are from 20 to 25 tc\.\x in diameter 

 with a few at 60 m[jL and a few 5 m[j.. 



Since the physical half-life of ^^^Au is 2-7 days and the biological half-life 

 of colloids is long compared with this period^, it is necessary to consider the 

 minimum permissible time-lapse between dosing with ^^^Au and transfusion 

 of bone marrow. We have set this minimum at four days, at which time 

 36 per cent of the administered ^^^Au remains. 



Replacement of bone marrow was attempted with homologous long-bone 

 marrow which had been passed through a succession of needles of decreasing 

 bore and diluted about 10 times with physiological saline. Administration 

 was by the ear vein and followed the sacrificing of the donor by not more 

 than one hour. No anticoagulant was used, and no case of embolism was 

 encountered in 36 transfusions. Nucleated cell counts of the transfusions 

 have indicated that each transfused rabbit received of the order of 10^ 

 nucleated cells per transfusion. 



As a precaution against possible infections the last three of five series of 

 rabbits were given intramuscular injections of streptomycin and penicillin. 



Measurements were made of body-weight, total white cell count, haemo- 

 globin concentration and total serum proteins. When any rabbit died, 

 specimens were taken of various soft tissues, notably liver, bone marrow, 

 spleen and whole-blood. These were weighed, digested in the cold with 



* Supplied by the United Kingdom Atomic Energy Authority Radiochemical Centre, 

 Amersham, England. 



57 



