Effectof Corynebacteriumparvumon Liver Proliferationand Regeneration1

The observation that Corynebacterium parvum (CP) ad ministration results in hepatomegaly prompted us to inves tigate the effect of that agent on hepatocyte proliferation in normal and partially hepatectomized matlivers. Its i.v. ad ministration to normal matswithintactliversresultedina significant increase in liver DNA synthesis (tritiated thymi dine uptake), total liver DNA, and liver weight, which were maximal at 4, 7, and 9 days, respectively. Both weight and DNA content remained elevated for at least 56 days after CP injection. Automadiogmaphy carried out at the time of maxi mal DNA synthesis indicated that hepatocyte proliferation contributed substantially to the increased tritiated thymi dine uptake. Histological examination of livers from treated animals revealed an increased number of Kupffer cells, macmophagegranuloma formation, and focal areas of he patocyte necrosis. When smaller doses of CP, which me suIted in less extensive histological changes, were used, increases in liver DNA synthesis, DNA content, and weight were similar to those occurring after use of a larger dose. The effect of CP was compared with that obtained when other immunomodulatoms were used. If a second injection of CP was administered at the time when DNA synthesis was maximal or when it had nearly returned to control values, further stimulation of DNA synthesis failed to occur. When CP was given 1 day before or after partial hepatec tomy, liver regeneration was greater than it was in untreated hepatectomized controls. Liver remnants at the time of partial hepatectomy were larger when CP had been admin istered 7 days previously than were those in untreated controls. Consequently, although liver weights at time of sacrifice were similar in the two groups, the percentage of regeneration was less in CP-treated animals. Such a finding further indicates that the hepatomegaly following CP is related to increased numbers of hepatocytes since liver regeneration is inversely related to the liver remnant follow ing partial hepatectomy. While liver damage resulting from CP administration may be responsible for the liver regener ation observed , other factors have been considered.