Multiparameter flow cytometric analysis of hepatic nuclear RNA and DNA of normal and hepatotoxin-treated mice.
Combined immunohistologic and flow cytometric methods were used to monitor the regenerative response of the mouse liver following intraperitoneal administration of the hepatonecrotic agent carbon tetrachloride (CCl4). A slight increase in the percentage of liver nuclei engaged in DNA synthesis (S-phase population) was evident 1 day after CCl4. The percentage of S-phase nuclei increased thereafter, lasting until day 6 after CCl4 with a peak at day 2 after CCl4. The method of sampling used (every 24 hours) places the period of maximal DNA synthetic activity between 48 hours and 72 hours after inoculation of the hepatonecrotic agent; at 48 hours the number of S-phase nuclei was approximately five times higher than the nonregenerating liver. Modified multiparametric flow cytofluorimetric analysis of hepatic nuclei indicated that early repopulation of the liver in response to CCl4-induced necrosis involved the selective proliferation of a specific subpopulation of liver cells which contained diploid nuclei of high RNA content. These nuclei were also observed in control animals, suggesting the existence of a subcompartment of 2C DNA content G1 hepatocytes potentially programmed for replacement proliferation.
D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000032:analysis*; D004261:DNA Replication / Q000187:drug effects; D005434:Flow Cytometry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012313:RNA / Q000032:analysis*
D012313:RNA; D004247:DNA; D002251:Carbon Tetrachloride