Transforming growth factor-[alpha] (TGF-[alpha]) improves hepatic DNA synthesis after hepatectomy in cirrhotic rats,

Abstract

Impaired liver regeneration in cirrhosis complicates the surgical treatment of liver tumors which arise in this setting. We developed a rat model to investigate the regenerative response of cirrhotic liver after hepatectomy and studied the effect of exogenous transforming growth factor-[alpha] (TGF-[alpha]), a potent liver mitogen. Micronodular cirrhosis was established by the simultaneous administration of CCl4 and phenobarbital. Hepatic DNA synthesis ([3H]thymidine incorporation into DNA) 24 hr after partial hepatectomy in cirrhotic rats was 15.6 +/- 3.4 cpm/[mu]g DNA (means +/- SEM), which was significantly lower than in normal rats (37.3 +/- 3.4 cpm/[mu]g DNA, P 3H]thymidine incorporation (35.6 +/- 8.2 cpm/[mu]g DNA, P < 0.05). An autoradiographic nuclear labeling index also confirmed increased DNA synthesis (6.7% vs 13.4%). TGF-[alpha] had no effect on normal regenerating liver (42.5 +/- 8.8 cpm/[mu]g DNA, NS). Although the significance of TGF-[alpha]-enhanced liver regeneration in cirrhosis has yet to be assessed, this model may be useful for the study of mechanisms which control hepatic proliferation.