Streaming liver VIII: cell production rates following partial hepatectomy

— Twenty-four young, female, random-bred rats weighing 250 g were partially hepatectomized and killed in groups of four animals at the following times: 1 h and 1, 2, 3, 7 and 14 days. One hour before killing, each rat was injected i.p. with 0.5 μCi [3H]-thymidine, specific activity 5 Ci/mmol/g body weight. Livers were processed histologically and dipped into liquid emulsion for autoradiography. Twenty-four hours after partial hepatectomy, hepatocyte and littoral labelling indices rose, reaching on the third day respective peak values of 3.7%, and 15.4%, whereupon they declined, remaining slightly above pre-treatment level. Labelling indices served for cell production estimates. On day 3 the hepatocyte labelling index rose 26-fold. At the same time hepatocytes doubled their ploidy, indicating that half of the observed L.I. increase was directed to DNA accumulation and not to cell division. The hepatocyte production rate therefore increased 13-fold (or 1300%). The acinus diameter increased 15%, and cell density declined 5%, so that the acinus capacity to retain cells increased only 5%. Since the acinus did not enlarge proportionally to cell production, it is concluded that 95% of newly formed cells were eliminated. Partial hepatectomy thus triggers two processes: an acute process lasting about a week marked by massive and rapid cell turnover during which most newly formed cells are eliminated; and a second, more protracted process which serves for liver mass restoration. It is proposed that partial hepatectomy induces an acute shortage of a hitherto unknown metabolite that is produced by newly formed cells immediately after hepatectomy.