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.