Some flow cytofluorimetric studies of the nuclear ploidy of mouse hepatocytes. II. Early changes in nuclear ploidy of mouse hepatocytes following carbon tetrachloride administration: evidence for polyploid nuclei arrested in telophase

Abstract

Mature mice have a large proportion of their hepatocyte nuclei in polyploid states (tetraploid and octaploid), and this is more prominent in females. We measured nuclear ploidy distribution cytometrically using ethidium bromide-stained hepatocyte nuclei liberated by in situ collagenase perfusion of the liver via the portal vein. After s.c. administration of 0.2 ml carbon tetrachloride the ploidy distributions of 8-month-old female mice changed from a control of 35% 2N, 45% 4N, and 20% 8N to 54% 2N, 45% 4N and 1% 8N at 6 h, and 65% 2N, 35% 4N and 0% 8N at 24 h. By 72 h 92% of the nuclei were diploid. These changes preceded any changes in mitotic index and S-phase index (3H-TdR autoradiographs). Histology confirmed the loss of higher-ploid nuclei but without mitotic figures or selective cell necrosis to account for the observations. Cleaved nuclei were prominent in sections of liver examined 3 h after CCl4 administration and suggested division of polypoid nuclei that had undergone prior segregation of chromatids and had presumably been arrested in telophase.