Hepatocytes were isolated from 1-day and 1,2,3 and 12-week old rat livers by collagenase perfusion and the relative numbers of albumin (ALB) and alpha-fetoprotein (AFP) producers were evaluated using the reverse hemolytic plaque assay. The percentage of ALB producers remained essentially constant to 35% over the 12-week period. In contrast, the percentage of AFP producers varied from 19% at 1 day up to 28% at 1 week and then down to 0.1% at 3 weeks. Moreover, a double identification of secreting hepatocytes, using an adaptation of the plaque assay, demonstrated that AFP producing hepatocytes were also ALB producers. These results are explained in terms of a restricted specialization of differentiating hepatocytes during normal development.
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