Cyclosporine, a powerful immunosuppressant, has been used successfully for organ transplantation. Its efficacy on liver transplants of patients with primary hepatic tumors remains controversial because of a high rate of recurrence of the original tumors in the transplanted livers. In this study, we experimentally tested whether cyclosporine exerts any effects on the growth of carcinogen-initiated liver cells using the short-term assays of rat liver carcinogenesis. Dietary cyclosporine, which maintained sufficient levels of blood cyclosporine and suppressed host immune functions, enhanced the development of the glutathione S-transferase, placental form-positive hepatocyte foci in the liver of male F-344 rats treated with a single weekly dose of diethylnitrosamine (75 mg/kg) for 3 wk. Dietary cyclosporine also accelerated the growth of preformed glutathione S-transferase, placental formpositive foci induced by a single dose of diethylnitrosamine (250 mg/kg) followed by the promoting regimen of a choline-deficient diet. It is possible that the enhancement of the size of hepatocyte foci by cyclosporine could be due to stimulation of growth or inhibition of regression. The mechanisms by which cyclosporine modifies the growth of preneoplastic lesions in the liver are not yet fully understood. Possible involvement of immunologically relevant cells in the liver, Kupffer cells and pit cells in the process is suggested. ( H E P m o L o c Y 1991; 13:304-309.)
Cyclosporine (CsA), discovered in 1972 (1, 2), has become the prototype of new immunosuppressants to aid successfully allograft survivals in organ transplantation, and its use in clinical medicine has now been extended to the treatment of various immune disorders (3, 4). As in the cases of conventional immunosuppressants, such as steroids and azathioprine, the use of CsA enhances the development of malignant lymphomas and other malignancies ( 5 ) . Clinical observations indicate that liver transplants in patients with primary liver tumors have been unsuccessful because of a high rate of recurrence of tumors in the recipient liver (6, 7).