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A variety of genetic alterations including gene mutations and chromosomal disorders have a critical role in cancer development. Activation-induced cytidine deaminase (AID) is capable of inducing nucleotide alterations in immunoglobulin genes and contributes to somatic hypermutation and class-switch recombination in B cells under physiological conditions. Although AID expression is tightly controlled because of its mutagenic potential, various types of pathogens and inflammation accompanied with the infection induce dysregulated and ectopic AID expression through the activation of the nuclear factor κB pathway. The constitutive aberrant AID expression causes the accumulation of nucleotide alterations and chromosomal abnormalities, leading to cancer development in various organs. Studies focused on the activity of aberrantly expressed AID provide a new insight into the mutagenic mechanisms during carcinogenesis.

Human cancer is a genetic disease resulting from the stepwise accumulation of genetic alterations in various tumor-related genes. Normal mutation rates, however, cannot account for the abundant genetic changes accumulated in tumor cells, suggesting that certain molecular mechanisms underlie such a large number of genetic alterations. Activation-induced cytidine deaminase (AID), a nucleotide-editing enzyme that triggers DNA alterations and double-strand DNA breaks in the immunoglobulin gene, has been identified in activated B lymphocytes. Recent studies revealed that AID-mediated genotoxic effects target not only immunoglobulin genes but also a variety of other genes in both B lymphocytes and non-lymphoid cells. Consistent with the finding that several transcription factors including nuclear factor-κB (NF-κB) mediate AID expression in B cells, proinflammatory cytokine stimulation of several types of gastrointestinal epithelial cells, such as gastric, colonic, hepatic, and biliary epithelium, induces aberrant AID expression through the NF-κB signaling pathway. In vivo studies revealed that constitutive AID expression promotes the tumorigenic pathway by enhancing the susceptibility to mutagenesis in a variety of epithelial organs. The activity of AID as a genome mutator provides a new avenue for studies aimed at understanding mutagenesis mechanisms during carcinogenesis.

Background/Aims Parenchymal hepatocytes (PHs) of rat contain colony-forming parenchymal hepatocytes (CF-PHs) as a small fraction. We aimed to demonstrate the presence of CF-PHs in humans and characterize them with respect to growth and differentiation potential. Methods Human PHs were co-cultured with Swiss 3T3 cells in the medium containing human serum, EGF, nicontinamide, and ascorbic acid 2-phosphate. To examine differentiation potential hepatocytes were cultured on gels of Matrigel Matrix. Results Few PHs formed colonies, the colony-forming efficiency being as low as 0.01–0.09%. The CF-PHs could be subcultured up to 7 passages. They showed a liver epithelial cell-like morphology, and immunocytochemically positive for albumin (ALB), cytokeratin (CK) 7, 8, 18, and 19 in a pre- and early phase-confluence, whereas they showed a typical differentiated hepatocyte-like morphology, and positive for α 1 -antitrypsin, but negative for CK7 and 19 in condensed regions at confluence. The CF-PHs at late confluence expressed mRNAs of ALB, HNF4, and isoforms of cytochrome P450 at low levels. However, when cultured on Matrigel, these cells expressed them at high levels comparable to those of original PHs. Conclusions We concluded that the human liver contains highly replicative hepatic progenitor-like cells as a minute population that retain a normal differentiation potential.