PRECURSOR-PRODUCT RELATIONSHIP BETWEEN OVAL CELLS AND HEPATOCYTES - COMPARISON BETWEEN TRITIATED-THYMIDINE AND BROMODEOXYURIDINE AS TRACERS

The expansion and differentiation of oval cells in the acetylaminofluo rene (AAF)/partial hepatectomy (PH) model was studied utilizing pulse- chase labeling with both tritiated thymidine ([H-3]TdR) and bromodeoxy uridine (BUdR), Animals in which a significant decrease in serum album in and increase in alanine aminotransferase and bilirubin were observe d demonstrated the most prominent differentiation of oval cells into h epatocytes. Administration of [H-3]TdR or BUdR, either individually or together, to the animals on day 6 after partial hepatectomy resulted in labeling of the majority of the oval cells by days 7 and 9 after PH , A striking difference in the distribution of [H-3]TdR- and BUdR-labe led cells in the double labeling experiments was observed on day 11, a t which time the number of [H-3]TdR-labeled cells increased 6-fold and that of double labeled cells decreased 2-fold, Furthermore, on day 11 the basophilic foci were weakly positive for BUdR and negative at lat er time points in animals receiving BUdR alone or together with [H-3]T dR, In contrast, the cells in basophilic foci as well as transitional cells were positive for [H-3]TdR, Cells heavily labeled with both [H-3 ]TdR and BUdR were present at all time points, indicating an inhibitio n of the proliferative activity, Pulse labeling of rat liver epithelia l cells with BUdR in vitro demonstrated that immunodetection of BUdR w as lost after three or more cell divisions. We conclude that the BUdR tagging method is particularly sensitive to label dilution during cell cycling and may not be suitable for establishment of a precursor-prod uct relationship between cell lineages when the progenitor population proliferates more than three times.