Timing of protooncogene expression varies in toxin-induced liver regeneration

Phyllis Schmiedeberg, Luis Biempica, Mark J. Czaja

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Hepatic expression of the protooncogenes c-fos and c-myc occurs within 2 h after partial hepatectomy, and these immediate early genes are thought to prime the hepatocytes for subsequent proliferation. To examine whether such gene activation occurred in the setting of hepatocyte proliferation after toxic liver injury, protooncogene expression was examined during the regenerative response fol-lowing liver injury from carbon tetrachloride (CCl4) or galactosamine (GaIN). The pattern of protooncogene expression after CCl4 mirrored that seen after partial hepatectomy, with rises in c-fos and c-myc mRNA content within 2 h, and then a rapid return to baseline levels. In contrast, early c-fos and c-myc expression did not occur after GaIN injury. Instead GaIN-induced regeneration led to a delayed, and prolonged c-fos and c-myc activation which peaked 24-48 h after injury. Increases in c-jun, jun-B, and jun-D mRNA levels also occurred in both models at times similar to the rises of c-fos and c-myc expression. Although the timing of DNA synthesis was identical after GaIN or CCl4 treatment, the proliferative response after GaIN injury was significantly less than that of CCl4, and marked by the histologic appearance of oval cells. The coadministration of 2-acetylaminofluorene, an inhibitor of differentiated hepatocyte proliferation, together with CCl4 altered the usual pattern of post-CCl4 protooncogene expression to one resembling that seen after GaIN injury. Thus, the timing of protooncogene expression during liver regeneration may vary considerably. These variations may influence the nature of the proliferative response in terms of which cell type(s) proliferates, and the amount of regeneration that ensues.

Original languageEnglish (US)
Pages (from-to)294-300
Number of pages7
JournalJournal of Cellular Physiology
Volume154
Issue number2
StatePublished - Feb 1993

Fingerprint

Galactosamine
Liver Regeneration
Liver
Wounds and Injuries
Hepatocytes
Hepatectomy
Regeneration
Genes
Chemical activation
2-Acetylaminofluorene
Messenger RNA
Immediate-Early Genes
Carbon Tetrachloride
Poisons
Transcriptional Activation
DNA

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Schmiedeberg, P., Biempica, L., & Czaja, M. J. (1993). Timing of protooncogene expression varies in toxin-induced liver regeneration. Journal of Cellular Physiology, 154(2), 294-300.

Timing of protooncogene expression varies in toxin-induced liver regeneration. / Schmiedeberg, Phyllis; Biempica, Luis; Czaja, Mark J.

In: Journal of Cellular Physiology, Vol. 154, No. 2, 02.1993, p. 294-300.

Research output: Contribution to journalArticle

Schmiedeberg, P, Biempica, L & Czaja, MJ 1993, 'Timing of protooncogene expression varies in toxin-induced liver regeneration', Journal of Cellular Physiology, vol. 154, no. 2, pp. 294-300.
Schmiedeberg, Phyllis ; Biempica, Luis ; Czaja, Mark J. / Timing of protooncogene expression varies in toxin-induced liver regeneration. In: Journal of Cellular Physiology. 1993 ; Vol. 154, No. 2. pp. 294-300.
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