Developmental expression of cytochrome p450s within intrasplenically transplanted fetal hepatocytes

Abstract

Fetal hepatocytes were harvested at day 20 of gestation from spontaneously hypertensive rats (SHR) and then transplanted into recipient adult SHR spleens. Morphological examination of the recipient spleens revealed that, after 4 and 10 wk, large masses of hepatocytes were present in the red pulp with apparent cord-like structures. Larger batches of hepatocytes were observed in the spleens at 10 wk after than at 4 wk after transplantation. Of major significance was the fact that hepatocyte transplanted spleens were able to express several families of cytochrome P450 (cyto P450) proteins 2–10 wk after transplantation. Immunochemical determinations revealed that cytos P450 IA1, P450 IIB1, P450 p, P450 HLp, and P450 LAto could be detected without any prior induction. All were intensely expressed 6 wk after transplantation; however, P450 IA1 and P450 IIB1 did not appear to be expressed by 2 wk after transplantation. Although cytos P450 p and P450 HLp did not appear to be expressed by 10 wk after transplantation, they were induced with dexamethasone at that time. Cyto P450 LAω and peroxisomal acyl CoA oxidase were expressed 6 wk after transplantation in a 70% hepatectomized host. These results demonstrate that fetal hepatocytes can be successfully transplanted into the spleens of recipients and that the fetal hepatocytes appear to grow and develop cyto P450 metabolizing systems.