@article{oai:sapmed.repo.nii.ac.jp:00014891,
 author = {長尾, 雅悦},
 issue = {1},
 journal = {札幌医学雑誌 = The Sapporo medical journal, The Sapporo medical journal},
 month = {Feb},
 note = {Tryptophan 2, 3-dioxygenase（TO, EC 1.13. 11. 11.）is a typical liver specific enzyme that appears in human liver postnatally and reaches to adult level 9 months after birth. In the primary culture of human hepatocytes, TO activity was not detected in the presence of 10-7 M dexamethasone and 2.5mM tryptophan after 6 days of culture. It was shown that the TO gene was switched-off in the human fetal liver at 14 to 20 weeks of gestation. Immunocytochemical staining of TO showed that TO was not expressed as early as the first day after birth by a few mature hepatocytes, and that the number of hepatocytes expressing TO gradually increased during the early neonatal development. In contrast, immature hepatocytes actively proliferated in the culture without growth factors or serum, showing a labeling index with [3H] thymidine of over 80% just after birth. Immature hepatocytes growth ability decreased rapidly with postnatal age. Double staining of hepatocytes from neonatal rat indicated that TO expressing cells and [3H] thymidine incorporated cells were sorted out from each other, suggesting immature hepatocytes proliferate, but do not express TO. Differentiated cells express TO, but lose their growth activity. When neonatal hepatocytes without TO were cultured on the feeder layer of adult rat hepatocytes for 3.5 days, expression of TO increased dramatically and reached 70% of the total cells. On the contrary, the feeder layer strongly inhibited the growth of neonatal hepatocytes. Other feeder layers such as non-parenchymal hepatocytes, Reuber hepatoma cells, and Swiss 3T3 fibroblasts, had no effect on the reciprocal modulation of terminal differentiation （TO expression） and growth of neonatal hepatocytes. Furthermore, neither conditione dmedium nor the extracellular matrix from primary culture of adult rat hepatocytes had any effect on the induction of cytodifferentiation of neonatal hepatocytes. “Dead" feeder layers of adult rat hepatocytes, obtained by treating the cells with cytosine arabinoside or drying them at 37℃, showed the same ability to induce cytodifferentiation of immature cells. When the dead feeder layers were treated with 1 N HCl and 0.1% trypsin, their ability to induce differentiation was almost completely lost. These results suggest that a cell surface component of adult rat hepatocytes, probably acid-labile protein, controls the terminal differentiation and the growth of immature hepatocytes.},
 pages = {1--12},
 title = {幼若肝細胞の分化誘導とTryptophan 2, 3-dioxygenase発現機構の研究},
 volume = {56},
 year = {1987}
}