Promoting effect of portocaval anastomosis in rat hepatocarcinogenesis

The effect of a surgical intervention, portocaval anastomosis (PCA) has been investigated in three different phases of a triphasic protocol of rat hepatocarcinogenesis. This protocol consists of the i.p. injection of 200 mg/kg of diethylnitrosamine (initiation) followed 2 weeks later by a 2 weeks diet with 2-acetylaminofluorene (2-AAF) and in the middle a necrogenic dose of CC14 (selection). One week later, a promoter such as phenobarbital (PB) is given chronically (promotion). PCA or a sham operation is performed 5 months before the end of the experiment. PCA alone does not induce hyperplastic nodules, nor does it when rats are initiated 5 weeks before. However, PCA alters the evolution of established nodules: it can act as a promoter like PB. Indeed, 5 months after initiation and selection, the number of rats bearing hepatocarcinomas is zero out of seven with a sham operation and six out of seven with PCA performed one week after the end of the selection. The combination of PCA and PB is more potent than PB or PCB alone since six out of six, five out of eight and six out of seven rats, respectively, bear malignant liver tumours. Thus PCA, which induces many systemic perturbations, has a promoting effect. This suggests that the chronic administration of a xenobiotic is not the only way to promote cancer development.