[Proliferation kinetics of bile duct epithelia in the regenerating mouse liver after CCl4-poisoning].

Autoradiographic and morphometric methods were used in studying the proliferation of interlobular bile duct epithelia of adult NMRI mice after CC14-poisoning (1 ml/kg i.p.). DNA synthesis starts on the 2nd day after CC14 administration. The time course of the 3H-thymidine labelling index is biphasic, with a first maximum at 2.5 and a second one 5 days after CC14 injection. An S-phase of 5.8 h was measured by 3H plus 14C-TdR double-labelling experiments. Proliferation is completed 10 days after CC14-poisoning, coinciding with the restitution of the liver parenchyma. Bile-duct epithelia remain diploid during the whole proliferative period, which suggests that every S-phase leads to mitotic division. The number of duct cells in portal cross sections remains constant. A quantitative model of the CC14- induced proliferation of interlobular bile duct cells is presented after calculating the total number of S-phases, the increase in cell number, and the final percentage of 3H-labelled nuclei (continuous infusion of 3H-TdR) as a function of time: With regard to 100 bile duct cells at the onset of proliferation 20 per cent S-phases occur during the first maximum and an additional 26 per cent occur during the second maximum of DNA SYNTHESIS, WHICH LEADS TO A 1.46-FOLD INCREASE IN CELL NUMBER. As derived from continuous 3H-TdR labelling (48 per cent 3H-labelled nuclei at the 6th day) and autoradiographic grain density measurements, the second wave of S-phases is due to DNA synthesis in ductular cells that have been formed during the first proliferative maximum. It is not possible to determine whether the proliferative activity observed is induced by lethal damage to bile-duct cells in the early course of CC14-poisoning, followed by compensatory growth and replacement of degenerate cells, or by nonspecific growth stimulation, inducing hyperplastic growth and elongation of terminal bile ducts.