Effect of caloric restriction on aflatoxin B 1-induced DNA synthesis, AFB 1-DNA binding and cell proliferation in Fischer 344 rats

Abstract

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 B 1(AFB 1) to hepatic or renal nuclear DNA and a reduction of AFB 1-induced hepatocellular damage. Repeated dosing of rats with AFB 1 resulted in the inhibition of hepatic and renal DNA synthesis measured by [ 3H]thymidine incorporation. However, the rate of DNA synthesis was greater in ad libitum (AL) rats than in calorically restricted (CR) animals. Three days after AFB 1 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. AFB 1 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 AFB 1 dosing. The rate of the regenerative cell proliferation was found to be slightly greater in AL rats than in CR animals. The AFB 1-induced regenerative DNA synthesis in both liver and kidney was retarded by CR.