Liver cell proliferation after partial hepatectomy in rats with liver metastases.

Objective: To validate proliferating cell nuclear antigen (PCNA) expression 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 hepatectomy or a sham operation. [3H]thymidine and 5-bromo-2'deoxyuridine (BrdU) incorporation, PCNA expression and flow cytometry were used to evaluate liver cell proliferation.

Results: The assessment of proliferating liver cells by PCNA expression and BrdU incorporation was more reliable than autoradiography. PCNA expression correlated well with BrdU incorporation (r = .68, P = .003) and autoradiography (r = .57, P = .02) in regenerating 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 livers of hepatectomized rats showed a higher proportion of S-phase nuclei as compared to S-phase nuclei in control rats. The correlation coefficients of the number of S-phase nuclei, BrdU-positive nuclei and PCNA-positive nuclei were .39 (P < .02) and .56 (P < .0005), respectively.

Conclusion: Flow cytometry and PCNA expression are simple and reliable methods of studying proliferation in metastases containing rat liver after partial hepatectomy.