RETROSPECTIVE ASSESSMENT OF LIVER-CELL PROLIFERATION VIA PCNA - A COMPARISON WITH TRITIATED-THYMIDINE

Cell proliferation (S phase response) in archival liver tissues of par tially hepatectomized rats was determined via proliferating cell nucle ar antigen (PCNA) immunohistochemistry. These results were compared wi th the S phase response assessed previously in the same tissues via tr itiated thymidine (Tdr) autoradiography. The effect of prolonged tissu e fixation on PCNA immunohistochemistry was compared in two studies: s tudy A, the liver was fixed for a maximum of 7 days and then embedded in paraffin and stored for similar to 18 months, while in study B, the liver was fixed in formalin for 7 years and then embedded in paraffin and stored for similar to 18 months until sectioning and immunostaini ng. PCNA immunostaining was successful in the liver sections of both s tudies, irrespective of the length of formalin fixation. Furthermore, the S phase labeling indices (LI) determined via PCNA and Tdr were com parable, although not identical, in the two studies. Therefore, use of PCNA immunohistochemistry should allow retrospective staining of rode nt tissues for the assessment of cell proliferative activity in formal in-fixed organs from previously conducted toxicity and carcinogenicity studies.