The influence of food intake on the development of diethylnitrosamine-induced liver tumours in mice

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Abstract
The aim of this study was to determine whether a dietary restriction, which significantly decreases body weight gain, also influences the development of diethylnitrosamine (DEN) induced liver tumours in Swiss mice. At birth, mice were in jected i.p. with a single dose of DEN (0.4 μmol/g body wt); negative control mice were sham injected. After weaning the animals received a stock diet either ad libitum (control group) or at 30% restriction (restricted group). A positive control group was fed ad libitum and received phenobarbital (500 p.p.m.) in their drinking water. At 12 weeks of age, glucose-6-phosphatase (G6Pase}-deficient foci were present in the liver of 80% of the control animals but only in 32% of the restricted group. Quantitatively, restricted animals had fewer foci per unit volume liver and these were smaller than in the control animals. By 36 weeks of age, hepatocarcinomas were seen in 100% of the control mice while in the restricted group there were no such mallgnant lesions and only 32% showed adenomas. The results clearly show that restriction of food intake inhibits promotion and progression of induced liver tumours. Amongst other uses, this model permits the study of the effect of dietary restriction on liver tumours, at an early stage.