Dietary modulation of rat liver carcinogenesis

Rat liver carcinogenesis was induced according to the resistant hepatocyte model of Solt and Farber. One week after the end of the procedure for the rapid growth of altered hepatocytes, one group of rats was submitted to a high fat (20%) regimen up to the end of the experiment. The incidence of histologically confirmed malignant hepatocarcinomas was compared with that observed in a group that remained on a normal diet. The modulating (promoting) effect of the high fat regimen was evident since nine out of 10 animals in this group bore macroscopically detectable tumors and eight out of 10 presented histologically confirmed hepatocellular carcinomas as early as 24 weeks after the beginning of the experiment. At that time, no malignant tumors were detected in the group submitted to the normal fat regimen. These results are similar to those resulting from a porto-caval shunt or the chronic administration of liver tumor promoters. This suggests that at this stage of the carcinogenic process, any treatment inducing chronically metabolic adaptation in a tissue containing preneoplastic nodules modulates positively the progression of these lesions as demonstrated by the dramatic reduction of the lag period for their malignant transformation.