The Effect of Portal Diversion on the Early Stages of Liver Carcinogenesis in the Rat

Abstract

The effect of portal diversion by ameroid constriction was studied in the carcinogenic process in the rat after initiation of foci by diethylnitrosamine and after the establishment of putative preneoplastic nodules. Portal diversion or portal diversion plus partial hepatectomy did not act to promote or select for the development of nodules. Furthermore, portal diversion did not alter the natural history of established nodules. These results suggest that vascular factors are not important at these early stages of the carcinogenic process in the rat liver.The theory of multistep progression of carcinogenesis in the liver has recently gained increasing prominence in the literature. Solt et al. (1) have demonstrated that small numbers of liver cells are altered by a single exposure to carcinogens such as diethylnitrosamine (DENA) and that the alteration is "fixed" by a round of cell proliferation. Once "initiation" occurs, these altered cells are capable of proliferation in an environment which inhibits growth of normal surrounding cells, allowing hyperplastic putative preneoplastic nodules to develop (2). The nodules are morphologically and histochemically different from the surrounding liver and are easily identifiable by y-glutamyl transpeptidase (GGT) staining (1, 3). The subsequent fate of the nodules is variable (3); the majority undergo a process of maturation and remodeling and eventually merge with the surrounding liver. A few persist and some develop into hepatocellular carcinomas.One problem with this model is that in order to "select" for development of nodules from initiated cells, conditions must be produced which stimulate liver proliferation but inhibit growth of the normal cells. Farber (2) has used a diet of 0.2% acetylaminofluorene (2-AAF) combined with partial hepatectomy or CCL administration. 2-AAF inhibits the growth of normal liver, but does not do so to the putative preneoplastic-initiated cells which are resistant to this agent (1, 4). 2-AAF is in itself a carcinogen, and this fact is one of the disadvantages of the model for some types of studies.A further problem is that there is variability in the