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 growth rate and h as been shown to delay the development of both spontaneous and induced neoplasia, In contrast to chronic food restriction, the extreme condi tion of fasting/refeeding is associated with an overall increase in ce ll turnover in several organs, including liver, compared with regular feeding, The present study was therefore designed to investigate the e ffect of complete food withdrawal followed by refeeding on the growth of hepatocyte nodules in initiated rat liver, Male Fischer 344 rats we re given a single dose of diethylnitrosamine (DEN, 200 mg/kg i.p.) and then, starting 1 wk later, they were exposed to one or three cycles o f fasting (3 days) followed by refeeding (11 days), The control group was fed continuously. Seven weeks after DEN administration all rats we re subjected to the resistant hepatocyte model (2-acetylaminofluorene coupled with CCl4) and 2 weeks later 2/3 partial hepatectomy (PH) was performed. All animals were killed 2 weeks after surgery. At PH rats g iven one cycle of fasting/refeeding had significantly larger glutathio ne S-transferase 7-7-positive hepatic lesions compared with controls ( mean area 0.73 +/- 0.04 versus 0.50 +/- 0.05 mm(2), P < 0.025; mean pe rcent area 25.6 +/- 3.2 versus 12.4 +/- 0.9, P < 0.005), while no sign ificant change was observed in their number, The observed differences were more pronounced with three cycles of fasting/refeeding, A similar pattern of results was obtained at the time of killing, It is conclud ed that fasting/refeeding can exert a positive effect on the growth of rat hepatocyte foci and nodules, in contrast to the general inhibitor y effect on carcinogenesis caused by food restriction.