150 BENSTED, BLACKETT, COUBTENAY, AND LAMERTON 



MATEKIALS AND METHODS 



In these studies male Fl hybrid rats (aged 6 to 8 weeks) of the inbred 

 August and Marshall strains have been used. The ^^P was given as intraperi- 

 toneal injections of sodium phosphate in saline with a specific activity between 

 1 and 4 ^c per [xg P. In the external radiation experiments one hmd limb was 

 irradiated, using 140 kVp radiation, half value layer 0-3 mm Cu, at a dose- 

 rate of about 50 r/mm, and one experiment where both hind limbs were 

 irradiated at 230 kVp, half value layer 1-5 mm Cu, at 20 r/min. In the ^sapu 

 experiments the injection was of Pu(N03)4 in nitric acid, which was brought 

 to about pH 5 with sodium carbonate solution immediately before injection. 



No spontaneous bone tumours have, so far, been observed in unirradiated 

 rats of the hybrid or parent strains. 



In the data to be presented there was, in some groups, an appreciable 

 mortality following irradiation from causes other than bone tumours. Since 

 the numbers of animals used are not sufficient to make a meaningful correc- 

 tion for this, both the time of appearance of bone tumours and mortality from 

 other causes (including non-skeletal tumours) are given. 



32p EXPERIMENTS 



The ^^P experiments have already been reported in some detail (Bensted 

 et al., 1961; Blackett, 1962). A very marked difference in the time of appear- 

 ance of tumours was found when repeated injections of ^^P were given. Figure 

 1 shows the mortality, with time of appearance of bone tumours (in groups of 

 about twenty animals) for a single injection of 3-0 ^c per g body weight, and 

 also for a total injection of 2-8 /xc/g given as a single injection of 1-0 /xc/g 

 followed by three injections of 0-6 /xc/g at two- weekly intervals. It can be 

 seen that with the single injection the first bone tumour appeared at eight 

 months after injection, the other five tumours in this group appearing between 

 eleven and thirteen months. AVith repeated injections the first tumour 

 appeared six months after the first injection and a further fifteen tumours by 

 ten months, without any deaths from other causes during this period. 



Earlier work (Blackett, 1962) had suggested that the time of appearance 

 of tumours was dependent on the precise timing of the repeated injections, 

 and in particular on whether the interval between the first and second injec- 

 tion was two, four or six weeks. Repetition of these experiments has given 

 inconsistent results and the effect of the timing must now be regarded as in 

 doubt. However, a marked difference between the effect of single and repeated 

 injections has been consistently demonstrated. 



The bone tumours have been found most frequently in the tibia and femur 

 and less frequently in the spine and humerus, and only very occasionally 

 elsewhere in the skeleton. 



