Transplantation of fetal liver tissue suspension into the spleens of adultsyngenic rats: effects of different cytotoxins on cytochrome P450 isoformsexpression and on glycogen content

Syngenic fetal liver tissue suspensions were transplanted into the spleens of adult male Fisher 344 inbred rats. Four months after surgery, transplant recipients and age matched control rats were treated with different cytoto xins (allyl alcohol [AAL], bromobenzene [BBZ], carbon tetrachloride [CCl4], or thioacetamide [TAA]) or the respective solvents 24 or 48 hours before s acrifice. Effects of the cy totoxins on the expression of three cytochrome P450 (P450) isoforms, 1A1, 2B1 and 3A2, within spleens and livers were asse ssed by immunohistochemistry. Additionally, effects on glycogen content wit hin the hepatocytes were examined. In the livers AAL caused small lesions and fatty degeneration of hepatocyte s only in some periportal areas. BBZ led to a perivenous necrosis of single cells only, whereas CCl4 and TAA caused complete necrosis of the centrilob ular parenchyma. Treatment with each of the four cytotoxins led to necrosis and fatty degeneration of single or groups of hepatocytes within the intra splenic transplants. This effect was most pronounced with CCl4 and TAA. The orthotopic livers of both solvent treated transplant recipients and con trol rats displayed only in few lobules a slight P450 1A1, but in all lobul es a strong P450 2B1 and 3A2 expression, all mainly located in the hepatocy tes around the central veins. AAL administration led to an increase in the P450 2B1 expression in the per ivenous hepatocytes, whereas the staining for P450 1A1 was not affected and that for P450 3A2 in the periportal areas was even decreased. BBZ administ ration caused a P450 1A1 expression in the peripor tal hepatocytes but a de crease in this staining of the perivenous cells. The number of hepatocytes positively stained for P450 2B1 and 3A2 in the perivenous and intermediate zones was diminished in comparison to the livers of solvent treated rats. T AA and, more pronounced, CCl4, administration caused a strong reduction in the expression of all three P450 isoforms. Spleens of control rats displayed almost no P450 isoforms expression, indep endent of the treatment with the cytotoxins. Similar to adult liver, the he patocytes in the transplant containing spleens showed nearly no P450 1A1, b ut a noticeable P450 2B1 and 3A2 expression. No staining was observed withi n the bile duct cells of the intrasplenic transplants. AAL administration slightly reduced the P450 2B1 and 3A2 expression in the transplants. BBZ and, much more pronounced, CCl4 and TAA treatment diminish ed the staining for all three P450 isoforms. AAL administration led to a marked decrease in the glycogen content of the hepatocytes of the periportal zones of the liver lobules, whereas after BBZ , CCl4 and TAA treatment a strong perivenous reduction in the glycogen cont ent was seen. Similarly, within the intrasplenic transplants a remarkable d ecline in the glycogen content of the hepatocytes was caused by the treatme nt with each of the four cytotoxins. Especially after AAL and BBZ treatment the glycogen depletion within both livers and transplants was much more pr onounced than the effects on morphology or P450 isoforms expression. It can be concluded that the effects of cytotoxins like AAL, BBZ, CCl4 or T AA seen in normal orthotopic liver are exerted in a similar way also in int rasplenic liver cell transplants.