Cytological changes in regenerating mouse liver.

Abstract

Summary and Conclusions Cytological studies of the liver of the mouse following partial hepatectomy suggest that the recovery period should be divided into two phases. First, there is a stage of rapid restoration of liver cells, essentially complete by the seventh day. Then there follows a period of about a month in which occur varying amounts of secondary regenerative activity, in many instances associated with focal necrosis. There is an impressively successful recovery in almost all instances. Apparently the focal necrosis delays but does not prevent this final recovery. Mitotic activity starts by the second day of regeneration and reaches a maximum on the third day. By the seventh day rapid cell multiplication is essentially completed. Mitotic activity is renewed sporadically when focal necrosis is present and replaces the cells lost. In the fully recovered livers no measurable mitotic activity is found. The number of binucleate liver cells decreases abruptly on the third day. This is demonstrated to be related to mitotic activity as follows: (a) binucleate cells divide as readily as do the mononucleate cells; but (b) relatively few of the mitotic divisions produce binucleate cells. Therefore, binucleate cells are lost, by mitotic division, at a greater rate than they are formed. There is an increase in binucleate cells following the cessation of mitotic activity. Possible reasons for this are discussed. The liver parenchymal cells are larger than normal during the period of greatest mitotic activity. This increase in size may be related to an increased water content of the cells, for the volume of both nuclei and cytoplasm is greater. From the fifth to seventh days, when the nuclear volume decreases, the cytoplasmic volume is even greater. Since the nucleolar volume increases strikingly on the fifth day, it is suggested that this is the time of major synthesis of new hepatic parenchymal cell cytoplasm. It is also at this time that the nucleo-cytoplasmic ratio begins to return to normal.