Evidence of clonal proliferation of hepatocytes after carbon-tetrachloride-induced hepatic injury in PGK-1 mosaic mice.
During aging processes, the liver is exposed continuously to both endogenous and exogenous chemicals which result in various degrees of hepatic damage. Hepatocytes maintain mitotic potential so that damaged cells are replaced by proliferation of selected clones of cells. Changes in the clonality after hepatic damage were investigated using carbon tetrachloride (CCl4) as a model hepatotoxin. The changes in clonality were determined by the alteration of the electrophoretic patterns of the allozyme, phosphoglycerate kinase-1A/1B (PGK-1A/1B), the locus of which is on the X-chromosome. In mammalian females random inactivation of one of the two X-chromosomes, of either paternal or maternal origin, are known to result in phenotype mosaicism. Heterozygous female (PGK-1a/1b) mice were obtained by crossing female (PGK-1b/1b) and male (PGK-1a/-) C3H/He mice. Liver samples were collected from these mice 5 days before (by biopsy) and 18 days after dosing with CCl4 (1 ml/kg, i.p.). Quantitative evaluation of the electrophoretic bands showed significant changes (percent change more than 7.2%, P less than 0.01) in the relative PGK-1A activity in 4 out of 10 cases. In one mouse a remarkable change, from 83.0 to 59.2%, was observed. Thus we concluded that selective hepatocyte proliferation occurs after cellular damage. We speculated that this process may play an important role in the aging of the liver.
Wada
Y
Y
Department of Hygiene, Akita University, School of Medicine, Japan.
Tsukada
M
M
Kamiyama
S
S
Koizumi
A
A
D000375:Aging / Q000502:physiology; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D002455:Cell Division; D056486:Chemical and Drug Induced Liver Injury; D002999:Clone Cells / Q000166:cytology / Q000201:enzymology*; D005260:Female; D014644:Genetic Variation; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008107:Liver Diseases / Q000201:enzymology*; D008115:Liver Regeneration; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D010735:Phosphoglycerate Kinase / Q000235:genetics* / Q000378:metabolism
D007527:Isoenzymes; D002251:Carbon Tetrachloride; D010735:Phosphoglycerate Kinase