EFFECTS OF DIETARY RESTRICTION ON INDUCTION OF UNSCHEDULED DNA-SYNTHESIS (UDS) AND REPLICATIVE DNA-SYNTHESIS (RDS) IN RAT-LIVER

The effects of dietary restriction on the induction of unscheduled DNA synthesis (UDS) and replicative DNA synthesis (RDS) were studied in t he hepatocytes of F344 rats exposed in vivo to dimethylnitrosamine (DM N) or CCl4. The animals were given food ad libitum, a restricted amoun t of food (4 g/rat/overnight) or no food. Hepatocytes were isolated 2 h after oral administration of DMN at a dose of 5 mg/kg body weight an d 48 h after oral administration of CCl4 at a dose of 400 mg/kg body w eight, and incubated for 4 h in Williams' medium E supplemented with e ither [H-3]thymidine for UDS or 5-bromodeoxyuridine for RDS. UDS was d etermined by autoradiography and RDS was determined by the immunoenzym atic staining method. The background levels of UDS (net grains/nucleus ) and RDS (cells in S phase) in control were - 12.4 and 0.64% for ad l ibitum feeding, -6.8 and 0.04% for restricted feeding, and -8.1 and 0% for fasting. UDS induced by DMN and RDS induced by CCl4 were 19.4 and 3.3% for ad libitum feeding, 34.5 and 10.4% for restricted feeding, a nd 47.8 and 15.1% for fasting. DMN demethylase activity in rat liver w as also found to increase with dietary restriction. These results indi cate that dietary restriction modulates the responses of UDS and RDS i n the liver of rats.