LIVER-CELL PROLIFERATION AFTER PARTIAL-HEPATECTOMY IN RATS WITH LIVERMETASTASES

OBJECTIVE: To validate proliferating cell nuclear antigen (PCNA) expre ssion and flow cytometry as proliferation markers in regenerating rat liver containing metastases. STUDY DESIGN: Rats containing colorectal liver metastases were killed at various days after 70% partial hepatec tomy or a sham operation. [H-3]thymidine and 5-bromo-2 'deoxyuridine ( BrdU) incorporation, PCNA expression and flow cytometry were used to e valuate liver cell proliferation. RESULTS: The assessment of prolifera ting liver cells by PCNA expression and BrdU incorporation was more re liable than autoradiography. PCNA expression correlated well with BrdU incorporation (r=.68, P=.003) and autoradiography (r=.57, P=.02) in r egenerating liver. BrdU incorporation and PCNA expression were higher in hepatectomized rats as compared to sham-operation rats at days 1-4 after hepatectomy. Flow cytometry of propidium-stained nuclei from liv ers of hepatectomized rats showed a higher proportion of S-phase nucle i as compared to S-phase nuclei in control rats. The correlation coeff icients of the number of S-phrase nuclei, BrdU-positive nuclei and PCN A-positive nuclei were .39 (P<.02) and .56 (P<.0005), respectively. CO NCLUSION: Flow cytometry and PCNA expression are simple and reliable m ethods of studying proliferation in metastases containing rat liver af ter partial hepatectomy.