DNA synthesis and cell proliferation in the simple liver acinus of 10 to 20-day-old rats: evidence for cell fusion.

Radioautography after 3H-thymidine injection, mitotic arrest by colchicine and camera lucida drawings were used to study DNA synthesis, mitosis, formation of binucleated cells and morphogenesis in the simple liver acinus of Rappaport in 10-20-day old rats. By ten days the arrangement of hepatic cell plates had already attained the adult configuration - irregular and thick in acinar zone 1 (periportal), straight and thin in acinar zone 3 (pericentral). The DNA synthetic index of parenchymal and bile duct cells slowly decreased during the observation period. Zonal labeling remained steady in the relationship: zone 1 greater than zone 2 greater than zone 3. Mitosis of parenchymal and bile duct cells reached a peak at 12 days, decreasing slowly thereafter. Mitosis also exhibited the relationship zone 1 greater than zone 2 greater than zone 3. The number of binucleated cells remained constant until after day 14 when it increased rapidly. Zonal distribution of binucleated cells was just the reverse of that for DNA synthesis and mitosis, that is zone 3 greater than zone 2 greater than zone 1. Radioautographic studies of binucleated cells labeled with 3H-thymidine indicated that a small percentage of them were formed by fusion of mononucleated cells. Conclusions are: (1) the 10-20-day old rat liver is expanding its cell population primarily in acinar zones 1 and 2 while overt differentiation is occurring in acinar zone 3, (2) ingestion of solid food around day 16 may be related to binucleated cell production due in part to altered portal venous blood changing the cellular microenvironments, (3) binucleated cells arise by suppression of cytokinesis, cell fusion and/or other non-mitotic routes.