Effects of a High-Sucrose Diet on the Development of Enzyme-altered Foci in Chemical Hepatocarcinogenesis in Rats¹

Dietary factors can modify metabolic events involved in the initiation, promotion, or progression of tumors. To determine whether a high-sucrose diet has any effect on the development of enzyme-altered foci during the promotion step of chemical hepatocarcinogenesis in rats, 1-day-old Sprague-Dawley rats were given a single i.p. dose of diethylnitrosamine; controls received an equivalent i.p. volume of 0.9% NaCl solution. At 21 days of age, the rats were weaned, segregated by sex, separated in groups, and fed modified AIN76A diets containing either 65% glucose or 65% sucrose, with or without 0.05% phenobarbital. At the end of a 4-week treatment period, the sucrose-fed control rats of either sex had significantly heavier livers than did those on the glucose diet. Enlarged livers were found also in the sucrose-fed diethylnitrosamine-treated female rats, which developed twice as many γ-glutamyltranspeptidase-positive foci per sq cm of liver section than did those on the glucose diet. Addition of phenobarbital augmented the number of foci 3-fold in the sucrose group and 5-fold in the glucose group. Focus count per sq cm was similar in animals on the two phenobarbital-supplemented diets. Despite the absence of statistically significant liver enlargement, results analogous to those in females were obtained in carcinogen-treated males. Differences between treatments, however, were smaller. In both female and male rats, the DNA-synthesizing activity of hepatocytes in enzyme-altered foci was significantly higher than in the surrounding normal parenchymal cells, as determined by autoradiography. These studies indicate that a high-sucrose diet has a promoting effect during hepatocarcinogenesis induced in the rat by diethylnitrosamine and that this effect is weaker than that of 0.05% phenobarbital.