Transgenic Mice

In transgenic mice bearing the Simian Virus 40 large T antigen under the control of the human antithrombin III regulatory sequences, a stepwise progression toward hepatocelular carcinoma is observed We have used two monoclonal antibodies (A6 and G7) developed against a surface antigen expressed in oval ceUsfrom dipintreated mice, to analyze the emergence of such preneoplastic populations in the livers of antithrombin III Simian Virus 40 T transgenic mice. We show thata uniquepopulation ofsmaUheterogenous epithelial ceUs, which probably corresponds to ovaland/or transitional ceUs according to their morphologicalfeatures, consistently appears at approximately the 10th week after birth and proliferates thereafter. This oval cell-like population stainedpositivelyforA6andG7monoclonal antibodies. Furthermore, different subpopulations usualy recognized as possible precursors ofcarcinoma ceUs including hyperplastic foci and neoplastic nodules as weU as carcinoma ceUs, were also positivefor A6 but not G7 monoclonal antibodies. Stimulation ofcellproliferation by partial hepatectomy performed at the time of emergence ofthe oval-like ceUs resulted in a rapid increase in the number of oval/transitional A6positive ceUs. Ourjftndings support the view that a common mechanism may be involved in the development of carcinomas that are induced by chemical carcinogens and in transgenic mice expressing apotent oncogene under the control ofa hepatic specific promoter. In addition, ourfjndings demonstrate a speciffc precursor-product relationship between the appearance ofthe oval/ transitional ceUs and the development ofneoplastic hepatocytes in this transgenic modeL (AmJ Pathol 1993, 143:1326-1336)

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