Intrahepatic polyamine levels during rat liver carcinogenesis induced by N-2-fluorenylacetamide

During a period of 200 days, the chronological changes of polyaminelevels (putrescine, spermidine and spermine) were observed inthe liver of adult female Sprague Dawley rats submitted to hepatocarcinogenesisby N-2-fluorenylacetamide (FAA). Three groups of 70 rats eachwere used: (1) Control 1: normal diet; (2) Control 2: low proteinand low riboflavin diet; and (3) Experimental: 0.06% FAA addedto the diet. No significant differences were noted for tissuelevels of the three polyamines when the two control groups werecompared. In contrast, considerable variations of these moleculeswere observed as a function of time in the FAA treated group:(a) an early and constant rise was seen in putrescine, with3 maxima at days 10, 60 and 150. This last peak was the highest:25 ± 6 nmol/g (8 times the value for the controls atthis time), and coincided with the appearance of cancerous lesions.(b) While spermidine levels varied during the experiment, nosignificant differences were noted in comparison with the controlgroups. Mean levels (nmol/g) were: 535 ± 108 Control1; 552 ± 95 Control 2; 633 ± 160 FAA-treated group,(c) Spermine levels were significantly lowered, with 3 minimacorresponding to the putrescine maxima. The lowest minima wasobserved on day 60: 114 ± 67 nmol/g, i.e., 4 times lowerthan the controls. This work shows that polyamine metabolismis profoundly modified during chemical carcinogenesis, but thepossible effect of polyamines on tumorigenesis itself cannotbe assessed at this point since modifications of polyamine levelsare probably also associated with phenomna of liver necrosisand compensatory tissue proliferation observed during the experiment.