Abstract
Pharmaceuticals, mostly nongenotoxic chemicals, induce neoplastic changes with relatively higher incidence in the rodents during chronic carcinogenicity bioassay. The liver is one of the most common target organs developing neoplasms and the results often give a serious impact on the development of new pharmaceuticals unless the results are appropriately interpreted as of non-relevance to human.
In this review article we have been trying to collect as many informations as possible to understand a complex and multistep process of carcinogenesis particular to hepatocarcinogenesis with interaction of pharmaceutical compounds as well as on the practical evidences helpful for risk assessment of pharmaceuticals for human use.
Carcinogenesis caused by pharmacodynamic and hormonal effects has been comparatively well elucidated with pharmaceuticals and not included in this article.
In this article, the following topics are discussed; predictive value of altered hepatocellular foci in some chronic carcinogenicity bioassay, phenobarbital type enzyme induction and tumor promotion, recently proposed mechanisms of carcinogenesis caused by peroxisome proliferators, role of apoptosis in hepatocarcinogenesis, and oncogenes, growth factors, and gap junctional intercellular communication in hepatocarcinogenesis.
