DEVELOPMENTAL EXPRESSION OF CYTOCHROME-P450S WITHIN INTRASPLENICALLY TRANSPLANTED FETAL HEPATOCYTES FROM SPONTANEOUSLY HYPERTENSIVE RATS

Fetal hepatocytes were harvested at 20 days of gestation from spontane ously hypertensive rats (SHR) and then transplanted into recipient adu lt SHR spleens. Morphological examination of the recipient spleens rev ealed that after 4 wk, large masses of hepatocytes were present in the red pulp with apparent cord-like structures. Of major significance wa s the fact that hepatocyte transplanted spleens were able to express s everal families of cytochrome P450 (cyto P450) proteins 2-6 wk after t ransplantation. Thus, the transplanted hepatocyte tissue appeared to g row and develop a cyto P450 metabolic system. Immunochemical determina tions revealed that cytos P450 IA1, P450 IIB1, P450 p, P450 HLp, and P 450 LAomega were over detected without any prior induction. None of th e cyto P450s could be detected in control nontransplanted spleens, how ever all were detected in fetal hepatocyte microsomes before transplan tation. All were intensely expressed 6 wk after transplantation, howev er P450 IA1 and P450 IIB1 did not appear to be expressed by 2 wk after transplantation. These results demonstrate that fetal hepatocytes can be successfully transplanted to the spleens of recipient hosts, and t hat the fetal hepatocytes appear to grow and develop functional cyto P 450 metabolizing systems. Therefore, transplantation of fetal hepatocy tes to splenic tissue represents a unique in vivo system of extra hepa tic metabolizing tissue.