EFFECT OF CALORIC RESTRICTION ON AFLATOXIN-B(1)-INDUCED DNA-SYNTHESIS, AFB(1)-DNA BINDING AND CELL-PROLIFERATION IN FISCHER-344 RATS

Young adult male Fischer rats maintained on a reduced calorie diet (60% of ad libitum food consumption) for 6 weeks showed a decrease in the binding of aflatoxin B1 (AFB1) to hepatic or renal nuclear DNA and a reduction of AFB1-induced hepatocellular damage. Repeated dosing of rats with AFB1 resulted in the inhibition of hepatic and renal DNA synthesis measured by [H-3]thymidine incorporation. However, the rate of DNA synthesis was greater in ad libitum (AL) rats than in calorically restricted (CR) animals. Three days after AFB1 dosing, the rate of DNA synthesis had recovered to the control level. Cell cycle analyses measured by a flow cytometric method on kidney cells of both AL and CR rats showed that there were no significant changes in cell populations in the S phase between these two groups of rats. AFB1 inhibited the cell proliferation on an average of 33%. The restoration of the cell proliferation in kidney cells was found on the third day after AFB1 dosing. The rate of the regenerative cell proliferation was found to be slightly greater in AL rats than in CR animals. The AFB1-induced regenerative DNA synthesis in both liver and kidney was retarded by CR.