Cellular analysis of c-Ha-ras gene expression in rat liver after CCl4 administration

Sasaki, Yutaka; Hayashi, Norio; Morita, Yasuhiro; Ito, Toshifumi; Kasahara, Akinori; Fusamoto, Hideyuki; Sato, Nobuhiro; Tohyama, Masaya; Kamada, Takenobu

doi:10.1002/hep.1840100416

Cited by 20 publications

(6 citation statements)

References 25 publications

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“…Oncogene induction appeared homogeneously distributed throughout the liver lobule, similar to the pattern of cellular activation described for c-jun during liver regeneration after partial hepatectomy in mice (4). This observation is in contrast with recent reports on oncogene activation during liver regeneration after toxic injury, in which a gradual centrifugal expression of cellular oncogenes from pericentral to periportal hepatocytes was described (23,26). These differences are very probably related to different mechanisms of cellular activation in these factor stimulation, activation of c-fos and c-jun during the AIR appears dissociated, with c-fos transcript accumulation at 4 h preceding c-jun activation at 8 h (see Fig.…”

Section: Discussioncontrasting

confidence: 99%

Activation of nuclear protooncogenes and alpha‐fetoprotein gene in rat liver during the acute inflammatory reaction

Bernuau

Moreau

et al. 1993

Liver

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ABSTRACT— Nuclear protooncogene and alpha‐fetoprotein gene expression is stimulated in hepatocytes during liver regeneration and by various growth factors in vitro. Metabolic adaptation of hepatocytes has been implicated in such gene reprogrammation. We examine here whether induction of an acute inflammation, a physiological situation of important metabolic adjustments, also triggers activation of nuclear oncogenes and of the AFP gene in rat liver. C‐fos, c‐jun and c‐myc mRNA accumulated on Northern blots between 4–12 h of inflammation and the steady‐state level of two small alpha‐fetoprotein transcripts characteristic of the adult liver increased at 4 h and 24 h of inflammation. In situ hybridization showed accumulation of the mRNA of the four genes studied in all hepatocytes, without any zonal lobular heterogeneity. 3H‐histoautoradiography and mitotic counts indicated an inhibition of DNA synthesis and mitosis, prolonged for at least 48 h after inflammation. Thus acute inflammation triggers the activation of nuclear protooncogenes and alpha‐fetoprotein gene in hepatocytes, but this activation is not followed by passage into the replicative cycle.

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Section: Discussioncontrasting

confidence: 99%

Activation of nuclear protooncogenes and alpha‐fetoprotein gene in rat liver during the acute inflammatory reaction

Bernuau

Moreau

et al. 1993

Liver

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“…A recent study on CC14-intoxicated rats showed that expression of the c-Ha-ras gene, which precedes cellular DNA duplication and cell division, increases markedly in the hepatocytes of the immediate perinecrotic parenchyma [34].…”

Section: Discussionmentioning

confidence: 99%

The nature and significance of liver cell vacuolation following hepatocellular injury ? an analysis based on observations on rats rendered tolerant to hepatotoxic damage

Nayak

Sathar

Mughal

et al. 1996

Vichows Archiv A Pathol Anat

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Swelling with nonlipid cytoplasmic vacuolation of diffusely distributed hepatocytes is seen consistently after mild acute and subacute liver injury. Several lines of evidence point to the possibility that this change may reflect a cellular adaptation beneficial to the host, rather than a degenerative change. The nature and significance of this morphological manifestation were tested in batches of albino rats given small doses of a variety of hepatotoxins, some of which were subsequently challenged with a large highly necrogenic dose of carbon tetrachloride (CCl4). Morphological and biochemical investigations showed that cytoplasmic vacuolation of liver cells following low doses of toxins was due to excess accumulation of glycogen, predominantly of the monoparticulate form. These cells lacked features of degeneration or regeneration and were much less susceptible to injury by the large dose CCl4, as assessed by structural and serum enzyme analyses. This tolerance to toxic damage seemed to be associated with excess accumulation of intracellular glycogen. We conclude from these and other observations on animal and human livers that many of the vacuolated hepatocytes seen in liver injury are cells adaptively altered to resist further insult rather than cells undergoing hydropic degeneration, as is commonly believed.

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“…Although toxin-induced liver injury also results in hepatic regeneration, protooncogene expression has been less studied in these models. This work (Goyette et al, 1984;Herbst et al, 1991;Sasaki et al, 1989) has been confined to isolated investigations of c-myc and ras expression after liver injury from carbon tetrachloride (CC1,). Yet, regeneration which occurs in the presence of hepatocellular injury may well differ from that seen in partial hepatectomy which involves the replication of undamaged hepatocytes.…”

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confidence: 99%

Timing of protooncogene expression varies in toxin‐induced liver regeneration

Schmiedeberg

Biempica

Czaja

1993

Journal Cellular Physiology

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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 following liver injury from carbon tetrachloride (CCl4) or galactosamine (GalN). 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 GalN injury. Instead GalN-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 GalN or CCl4 treatment, the proliferative response after GalN 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 GalN 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.

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Cellular analysis of c-Ha-ras gene expression in rat liver after CCl4 administration

Cited by 20 publications

References 25 publications

Activation of nuclear protooncogenes and alpha‐fetoprotein gene in rat liver during the acute inflammatory reaction

Activation of nuclear protooncogenes and alpha‐fetoprotein gene in rat liver during the acute inflammatory reaction

The nature and significance of liver cell vacuolation following hepatocellular injury ? an analysis based on observations on rats rendered tolerant to hepatotoxic damage

Timing of protooncogene expression varies in toxin‐induced liver regeneration

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