Transcriptional switch from albumin to .alpha.-fetoprotein and changes in transcription of other genes during carbon tetrachloride-induced liver regeneration

Panduro, Arturo; Shalaby, Fouad; Weiner, Francis R.; Biempica, Luis; Zern, Mark Α.; Shafritz, David A.

doi:10.1021/bi00354a034

Cited by 127 publications

(77 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well established that hepatocellular regeneration is induced biphasically at 6 hr and at 36-48 hr after administration of the protective dose ofCC1, (22,24,27,28,33,48). This protective dose stimulates the resting hepatocytes (Go) to enter S-phase of cell cycle within 2 hr (19,20,24).…”

Section: Discussionmentioning

confidence: 99%

Effect of Phenobarbital and Mirex Pretreatments on CCl₄ Autoprotection

Thakore

Mehendale

1994

Toxicol Pathol

View full text Add to dashboard Cite

Male Sprague-Dawley rats maintained on either normal diet (N) or on a diet containing phenobarbital (PB 225 ppm) or mirex (M; 10 ppm) for 15 days received either corn oil or 1 single administration of a protective dose of CCI, (0.3 mVkg, PO) on day 16. At 24, 48, 72,96, or 144 hr after the protective dose, a high dose of CCI, (5 mVkg, PO) was administered to rats of all the groups, and they were observed for 14-day lethality. In a second experiment, in rats maintained on N, PB, or M diet, liver microsomal cytochromes P-450, aminopyrine demethylase, and aniline hydroxylase were measured at various time points after the administration of the protective dose of CCl,. Serum aspartate transaminase, alanine transaminase, and sorbitol dehydrogenase elevations and histopathological changes observed under a light microscope were used as toxic end points to assess hepatotoxicity. Autoprotection was 100% when the high dose was given at 24 hr after the protective dose in N rats, whereas it was only 55% in PB-or M-pretreated rats. For later time points of 48,72, and 96 hr, autoprotection was only around 50% in N rats, whereas it was almost 100% in PB-and M-pretreated rats. When the high dose was administered at 144 hr after the protective dose, autoprotection further declined to 25% in N rats and to 75% in M-treated rats, but it remained at 100% in PB-treated rats. The liver microsomal cytochromes P-450, aminopyrine demethylase, and aniline hydroxylase were induced in rats after the dietary treatment with PB or M when compared to the rats on N diet. However, after administration of the protective dose of CCl, to these rats, these enzyme activities were decreased in all the groups at 24 hr after the protective dose, persisted at a low level even at the 72-hr time point, and then slowly recovered to normal by 120 hr. Liver injury was evident by serum enzyme elevations and histopathological changes in all the groups at 24 hr after the protective dose, but the injury was progressive in PB-and M-treated rats with maximum injury at 48 hr, injury in PB-treated rats being greater than that in M-treated rats. The livers recovered completely in all the groups by 120 hr as revealed by serum enzymes and liver histology. The levels of microsomal enzymes at various time points after the protective dose in N, PB, and M treatment groups correlate neither with liver toxicity nor with animal survival after the administration of the large dose of CCl,. Therefore, a postponement of the hepatocellular regeneration stimulated by the protective dose of CCl, caused by prior exposure to PB and M, as reported earlier, appears to play a role in the correspondingly postponed maximal expression of CCl, autoprotection. Furthermore, the prolongation ofautoprotection by M and even greater effect by PB appears to be related to the greater stimulation of hepatocellular proliferation and augmented tissue repair processes attributable to the protective dose of CCl, reported previously.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Phenobarbital and Mirex Pretreatments on CCl₄ Autoprotection

Thakore

Mehendale

1994

Toxicol Pathol

View full text Add to dashboard Cite

show abstract

“…This reaction is similar to that observed when the liver is exposed to certain necrotic agents such as carbon tetrachloride. 21,22 These observations combine to suggest that the cellular regenerative response observed in DAPM/RP animals is indistinguishable from that seen in RP animals. SHPC clusters are never observed in DAPM/PH, DMSO/PH, DAPM-only, or DMSOonly control rats (Fig.…”

Section: Dapm Treatment Produces Severe Bile Ductmentioning

confidence: 91%

Bile duct destruction by 4,4′-diaminodiphenylmethane does not block the small hepatocyte-like progenitor cell response in retrorsine-exposed rats

Best

Coleman

2007

Hepatology

View full text Add to dashboard Cite

Liver regeneration after surgical partial hepatectomy (PH) in retrorsine-exposed rats is accomplished through the outgrowth and expansion of small hepatocyte-like progenitor cells (SHPCs). The cells of origin for SHPCs and their tissue niche have not been identified. Nevertheless, some investigators have suggested that SHPCs may represent an intermediate or transitional cell type between oval cells and mature hepatocytes, rather than a distinct progenitor cell population. We investigated this possibility through the targeted elimination of oval cell proliferation secondary to bile duct destruction in retrorsine-exposed rats treated with 4,4-diaminodiphenylmethane (DAPM). Fischer 344 rats were treated with 2 doses (30 mg/kg body weight) retrorsine (at 6 and 8 weeks of age) followed by PH 5 weeks later. Twenty-four hours before PH, select animals were given a single dose of DAPM (50 mg/kg). Treatment of rats with DAPM produced severe bile duct damage but did not block liver regeneration. Oval cells were never seen in the livers of DAPM-treated retrorsine-exposed rats after PH. Rather, liver regeneration in these rats was mediated by the proliferation of SHPCs, and the cellular response was indistinguishable from that observed in retrorsineexposed rats after PH.

show abstract

“…[52][53][54] In this case, transient elevation of ␣-fetoprotein (AFP) in the blood may be the result of production by proliferating hepatocytes adjacent to the necrotic zone, 55 which switch from albumin to AFP production. 56 There is little, if any, evidence of proliferation of ductal or periportal oval cells. However, identification of proliferating cells by BrdU reveals labeling of small periductular cells, suggesting some participation of putative liver stem cells 57 (Engelhardt NV, Sell S, unpublished data, 1989; Fig.…”

Section: Injury Modelsmentioning

confidence: 99%

Heterogeneity and plasticity of hepatocyte lineage cells

2001

View full text Add to dashboard Cite

It is hypothesized that the liver has 3 levels of cells in the hepatic lineage that respond to injury or carcinogenesis: 1) the mature hepatocyte, which responds to partial hepatectomy (PH), to centrolobular injury, such as that induced by carbon tetrachloride (CCl 4 ), and to dimethylnitrosamine (DEN) hepatocarcinogenesis; 2) the ductular "bipolar" progenitor cell, which responds to centrolobular injury when the proliferation of hepatocytes is inhibited, and to N-2-acetylaminofluorene (AAF) hepatocarcinogenesis; and 3) the putative periductular stem cell, which responds to periportal injury, such as induced by allyl alcohol and to choline-deficiency models of hepatocarcinogenesis. Hepatocytes are numerous, respond rapidly by 1 or 2 cell cycles, but can only produce other hepatocytes. The ductular progenitor cells are less numerous, may proliferate for longer times than hepatocytes, and are generally considered "bipolar," i. The restitutive response of the liver to different injuries involves proliferation of cells at different levels in the liver lineage. The hypothesis presented by this review is that, similar to other organ systems, the cellular lineage of the liver consists of stem cells, precursor cells (transit-amplifying cells), and mature cells. It is also proposed that there are 2 origins of stem cells in the liver: endogenous and exogenous. 1

show abstract

Transcriptional switch from albumin to .alpha.-fetoprotein and changes in transcription of other genes during carbon tetrachloride-induced liver regeneration

Cited by 127 publications

References 37 publications

Effect of Phenobarbital and Mirex Pretreatments on CCl₄ Autoprotection

Effect of Phenobarbital and Mirex Pretreatments on CCl₄ Autoprotection

Bile duct destruction by 4,4′-diaminodiphenylmethane does not block the small hepatocyte-like progenitor cell response in retrorsine-exposed rats

Heterogeneity and plasticity of hepatocyte lineage cells

Contact Info

Product

Resources

About

Transcriptional switch from albumin to .alpha.-fetoprotein and changes in transcription of other genes during carbon tetrachloride-induced liver regeneration

Cited by 127 publications

References 37 publications

Effect of Phenobarbital and Mirex Pretreatments on CCl4 Autoprotection

Effect of Phenobarbital and Mirex Pretreatments on CCl4 Autoprotection

Bile duct destruction by 4,4′-diaminodiphenylmethane does not block the small hepatocyte-like progenitor cell response in retrorsine-exposed rats

Heterogeneity and plasticity of hepatocyte lineage cells

Contact Info

Product

Resources

About

Effect of Phenobarbital and Mirex Pretreatments on CCl₄ Autoprotection

Effect of Phenobarbital and Mirex Pretreatments on CCl₄ Autoprotection