Hormonal and hormone-like effects eliciting hepatocarcinogenesis

In various species, the manifestation of hepatocellular neoplasms is regularly preceded by preneoplastic foci of altered hepatocytes (FAH), the cellular phenotype of which is strikingly similar in experimental and human hepatocarcinogenesis, irrespective of the etiology of this process. The different types of FAH have been related to three main preneoplastic hepatocellular lineages: 1) the glycogenotic-basophilic cell lineage, 2) its xenomorphic-tigroid cell variant, and 3) the amphophilic-basophilic cell lineage. The predominant glycogenotic-basophilic and tigroid cell lineages developed especially after exposure to DNA-reactive chemicals, radiation, viruses, transgenic oncogenes and local hyperinsulinism. The early phenotypes of these lineages indicate an initiation by insulin or insulinomimetic effects of the oncogenic agents, triggering the raf-Map kinase signal transduction pathway. In contrast, the amphophilic-basophilic cell lineage has mainly been observed after exposure of rodents to not directly DNA-reactive peroxisome proliferators but also hepadnaviridae, its biochemical pattern mimiking an effect of thyroid hormone.