Establishment of an in vivo highly metastatic rat hepatocellular carcinomamodel

We previously found by chance that N-nitrosomorpholine (NMOR) given after a multi-carcinogenic treatment induces liver carcinomas with 56% lung metast asis, and it nas confirmed that hepatocellular carcinoma (HCC) with 100% lu ng metastasis was produced by 24-week treatment with NMOR and additional tr eatment,vith diethylnitrosamine (DEN) In the present study, we modified the duration of NMOR to establish an animal model with a simple experimental p rotocol and an appropriate experimental duration which would facilitate fur ther study of the mechanisms of metastasis and antimetastatic agents. The r esults revealed BEN exposure followed by a 16-week treatment with NMOR to b e a most efficient method for the induction of HCC metastasizing to the lun g, Loss of cadherin, demonstrated immunohistochemically; occurred in on ear ly stage of carcinogenesis, and this was reflected in malignant conversion of primary lesions. This model, with its essential similarities to malignan t tumor behavior in man, should find application not only for elucidation o f the mechanisms underlying metastasis, but also in the development of anti -metastatic agents.