The enhancing effect of fasting/refeeding on the growth of nodules selectable by the resistant hepatocyte model in rat liver

Caloric restriction causes a generalized decrease in growthrate and has been shown to delay the development of both spontaneousand induced neoplasia. In contrast to chronic food restriction,the extreme condition of fasting/refeeding is associated withan overall increase in cell turnover in several organs, includingliver, compared with regular feeding. The present study wastherefore designed to investigate the effect of complete foodwithdrawal followed by refeeding on the growth of hepatocytenodules in initiated rat liver. Male Fischer 344 rats were givena single dose of diethylnitrosamine (DEN, 200 mg/kg i.p.) andthen, starting 1 wk later, they were exposed to one or threecycles of fasting (3 days) followed by refeeding (11 days).The control group was fed continuously. Seven weeks after DENadministration all rats were subjected to the resistant hepatocytemodel (2-acetylaminofluorene coupled with CCl₄) and 2 weekslater 2/3 partial hepatectomy (PH) was performed. All animalswere killed 2 weeks after surgery. At PH rats given one cycleof fasting/refeeding had significantly larger glutathione S-transferase7–7-positive hepatic lesions compared with controls (meanarea 0.73 ± 0.04 versus 050 ± 0.05 mm², P <0.025; mean percent area 25.6 ± 3.2 versus 12.4 ±0.9, P < 0.005), while no significant change was observedin their number. The observed differences were more pronouncedwith three cycles of fasting/ refeeding. A similar pattern ofresults was obtained at the time of killing. It is concludedthat fasting/refeeding can exert a positive effect on the growthof rat hepatocyte foci and nodules, in contrast to the generalinhibitory effect on carcinogenesis caused by food restriction.