BROMODEOXYURIDINE UPTAKE BY EARLY LIVER METASTASES IN RATS - A COMPARISON OF THE HEPATIC-ARTERY AND PORTAL-VEIN INFUSION ROUTES

Liver metastases generated by the intraportal inoculation of ascites h epatoma cells in Donryu rats were labeled with bromodeoxyuridine (BrdU ) through the hepatic artery, or through the portal vein with or witho ut ligation of the hepatic artery, 3, 6, or 9 days after tumor inocula tion. The distribution of BrdU-labeled cells was evaluated in 174 meta stases, 110-1640 mu m in diameter, by immunohistochemical methods, Whe n a dual blood supply from the portal vein and hepatic artery existed, the BrdU-labeled cells mere diffusely found in the metastases regardl ess of their size and the route of BrdU infusion, When blood supply to metastases larger than 610 mu m in diameter was from a single source, namely the portal vein, the BrdU-labeled cells were located within 90 -290 mu m from the margin of the metastases. These results indicate fi rst, that drug uptake by the inner part of the early metastatic liver tumors is achieved through the hepatic artery, and second, that drug u ptake by early liver metastases through the portal vein is limited to within the extent of portal diffusion regardless of the size of the me tastases, Thus, we conclude that prophylactic treatment against liver metastases would be more effective when given via the hepatic artery r oute rather than via the portal vein route.