230 TORE HULTIN et ttl. 



the microsomes from aminofluorene-treated animals showed a considerably 

 higher incorporation activity per unit amount of RNA than did normal 

 microsomes. With isolated RNP-particles, however, the stimulation effect 

 was less pronounced. 



There may be some relationship between the effects of 2-aminofluorene 

 and its carcinogenic potency. In guinea-pigs, a species refractory to the 

 carcinogenic action of 2-aminofluorene, the activation after 20 hr. was 

 smaller than in rats (Table V). On the other hand, a significant stimulation 

 was repeatedly observed after 4-6 hr., i.e. at a period when rat liver 

 microsomes showed a definite inhibition. This species difference may 

 possibly be due to the more rapid disposal of aminofluorene by metabolic 

 detoxication in the guinea-pig liver. It may be of some interest that the 

 well-known bladder carcinogen 2-aminonaphthalene, which has some 

 potency also in liver, had about the same effects in rat liver as 2-amino- 

 fluorene (Table V). 



TABLE VI 



Effect of in vivo Treatment with 2-Aminofluorene or X-Rays on the 

 Glycogen Content of Rat Liver 



Dose of 2-aminofluorene 25 mmoles/kg. body weight, and of X-rays (all 

 body irradiation, 45 min.) 2500 r. Glycogen content [16] in per cent of liver dry 

 weight. 



Treatment of rats Glycogen content 



Fed ad libitum 9 • i 



Fasted 20 hr. 0"53 



Fasted 45 hr. 0-43 



Fasted 24 hr. Aminofluorene 4 hr. i '51 



Fasted 45 hr. Aminofluorene 21 hr. 3 '26 



Fasted 45 hr. X-rays 21 hr. 61 



As a routine the experiments were carried out with animals which had 

 been kept without food for i6~20 hr. By this brief period of starvation the 

 glycogen content in the liver is greatly reduced, a fact of practical advantage 

 in the preparation of microsomes and RNP-particles. In the animals treated 

 with 2-aminofluorene it was observed that the content of liver glycogen 

 was higher than in the controls, without reaching, however, the level 

 characteristic of normal, fed animals (Table VI). A similarly increased 

 glycogen content has been observed by Kay and Entenman [15] in X-ray 

 irradiated rats. In view of this striking similarity it seemed pertinent to 

 find out whether X-ray treatment would also evoke an increased activity 

 of amino acid incorporation in vitro As is shown by Table VII the in- 

 corporation activity of mitochondria-free rat liver homogenates was in 

 fact increased 21 hr. after the exposure of the animals to an X-ray dose 

 of 2500 r. 



