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Effect of Corynebacterium parvum on Liver Proliferation and Regeneration¹

Department of Surgery, University of Pittsburgh School of Medicine [B.F., M.C.G., E.A.S.], and Department of Pathology, Shadyside Hospital [E.R.F.], Pittsburgh, Pennsylvania 15261

The observation that Corynebacterium parvum (CP) administration results in hepatomegaly prompted us to investigate the effect of that agent on hepatocyte proliferation in normal and partially hepatectomized rat livers. Its i.v. administration to normal rats with intact livers resulted in a significant increase in liver DNA synthesis (tritiated thymidine 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. Autoradiography carried out at the time of maximal DNA synthesis indicated that hepatocyte proliferation contributed substantially to the increased tritiated thymidine uptake. Histological examination of livers from treated animals revealed an increased number of Kupffer cells, macrophage granuloma formation, and focal areas of hepatocyte necrosis. When smaller doses of CP, which resulted 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 immunomodulators 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 hepatectomy, 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 administered 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 following partial hepatectomy. While liver damage resulting from CP administration may be responsible for the liver regeneration observed, other factors have been considered.

¹ Supported by USPHS Grant AM-13228.

² To whom requests for reprints should be addressed, at Department of Surgery, University of Pittsburgh School of Medicine, 914 Scaife Hall, 3550 Terrace Street, Pittsburgh, Pa. 15261.

Received 7/19/78. Accepted 1/12/79.