Influence of calorie restriction on oncogene expression and DNA synthesis during liver regeneration

Controlling calorie intake (CCI) extends healthful life-span by a mechanism that may involve reduced rates of cell division without detriment to inducible cellular responses. To test whether inducible cellular proliferation is preserved by CCI and whether the mRNA expression levels of oncogenes activated by cell division can be reduced by CCI, we evaluated the effect of dietary energy on the hepatocellular proliferative burst and on oncogene and growth factor mRNA expression induced by partial hepatectomy. Eighty Fischer 344 rats were separated into two dietary groups and were fed semipurified diets for 10 weeks that differed only in calories by 40%. Mean hepatic levels of [3H]thymidine incorporation were greater among CCI animals at 18, 24, 28, and 36 hr after partial hepatectomy. The expression of c-fos and c-Ki-ras mRNAs, activated during hepatic regeneration, was reduced by CCI. Peak expression of c-fos among ad libitum fed controls to levels 4-6 times greater than prehepatectomy levels was not detected among CCI animals. Protracted elevated expression of c-Ki-ras among ad libitum fed animals was foreshortened by CCI. These findings demonstrate that inducible cellular proliferative responses are preserved by CCI and that the mRNA expression levels of c-fos and c-Ki-ras activated during cell division are reduced by controlling dietary energy. Preserved inducible cellular responses and lowered oncogene expression during cell division may be attributes of the healthful protective effect of CCI.