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N Fausto

Publications and source records attributed to N Fausto.

At least 109 records · Page 6Linked to original sources
PubMed1983

alpha-Fetoprotein and albumin mRNA levels in liver regeneration and carcinogenesis.

Using a titration procedure, we measured the proportion of alpha-fetoprotein (AFP) and albumin mRNA in normal, regenerating, and preneoplastic rat livers. AFP mRNA constitutes approximately 0.006% of the polysomal polyadenylated RNA of normal livers and this proportion increases only slightly before the onset of DNA synthesis in liver regeneration induced by partial hepatectomy or CCl4 injury. In either model of liver regeneration, the proportion of AFP mRNA in polysomal RNA is highest approximately 24 h after the peak of DNA synthesis. The increase in the proportion of AFP mRNA in polysomal RNA is relatively small during liver regeneration (2-4-fold) but is larger (30-50-fold) in preneoplastic livers of rats fed a choline-deficient diet containing 0.1% ethionine. In contrast to those changes in AFP mRNA, albumin mRNA levels remain unchanged during liver regeneration and double in preneoplastic livers. Our results indicate that the concept of "retrodifferentiation" as it applies to liver regeneration and certain types of hepatic neoplasia needs reevaluation.

Albumins↗
PubMed1983

Expression of a cellular oncogene during liver regeneration.

The number of transcripts of the cellular oncogene ras, which is homologous to the transforming gene of Harvey sarcoma virus, increases during liver regeneration in rats. The increase in these transcripts in liver polysomal polyadenylated RNA occurs at the time of activation of DNA synthesis during the regenerative process induced by partial hepatectomy or carbon tetrachloride injury. The number of ras transcripts returns to basal levels within 72 hours. These observations show that transcription of a cellular oncogene increases in a regulated way in a nonneoplastic growth process.

Animals↗
PubMed1981

Alterations in polyadenylated messenger ribonucleic acid from free and total polysomes of a rat hepatoma.

We examined the homology between polysomal polyadenylated ribonucleic acid (mRNA) populations of hepatoma 252, a tumor which is deficient in the synthesis of plasma proteins, and those of normal and regenerating rat liver. Hybridization of polyadenylated mRNA populations with homologous or heterologous complementary deoxyribonucleic acids showed that mRNA from total and free polysomes from hepatoma 252 lack sequences which are present in normal or regenerating liver. Although there are obvious differences in the abundance of sequences between tumor and normal or regenerating liver polysomal mRNA, we did not detect, with the techniques used in this work, tumor-specific sequences. Analysis of hybridization curves using derivative plots did not reveal the presence in tumor mRNA of a high complexity class not present in normal liver. We conclude that alterations in mRNA populations of free and total polysomes of this tumor primarily reflect processes of genetic restriction rather than the derepression of previously unexpressed genes.

Animals↗
PubMed1981

Separation of two populations of cells with gamma-glutamyl transpeptidase from carcinogen-treated rat liver.

Noninbred Sprague-Dawley rats were maintained on a choline-deficient diet containing 0.05% ethionine. After 10-13 weeks, livers were dispersed with collagenase, lysozyme, collagenase and hyaluronidase. Pronase, or a selected batch of trypsin. The highest yield of cells with histochemically demonstrable gamma-glutamyl transpeptidase (GGT) was obtained with trypsin. After velocity sedimentation in an isokinetic gradient of Ficoll in tissue culture medium, two modal populations of cells with histochemically demonstrable GGT were observed. The first mode contained cells that were morphologically different from hepatocytes and that may be oval cells. The second, more rapidly sedimenting modal population of cells with GGT was morphologically similar to hepatocytes as assessed with Wright's stain; the location of this population in the gradient was the same as the location of cells with the appearance of hepatocytes that lacked iron and that had decreased glucose 6-phosphatase. In multiple experiments, the purest fractions contained 71.7 +/- 3.5% cells (mean +/- SD) with the appearance of hepatocytes with histochemically demonstrable GGT.

Animals↗
PubMed1981

On the existence of variant forms of gamma-glutamyl transferase in regenerating and neoplastic liver.

We attempted to identify variants of gamma-glutamyl transferase (GGT) which may differ in their affinity for Concanavalin A (Con A) in extracts of fetal, regenerating, neoplastic and normal adult rat liver. GGT activity was low in normal liver and did not increase after partial hepatectomy. Feeding a choline-deficient diet containing 0.05% ethionine caused a large increase in hepatic GGT activity which persisted throughout the feeding period of 23 weeks. Practically all of the GGT contained in extracts prepared with Triton X-100 from fetal, regenerating, pre-neoplastic and neoplastic rat liver as well as that from normal adult liver bound to Con A-Sepharose and was eluted from the columns with methyl-alpha-D-mannopyranoside. In contrast, GGT from bovine kidney extracts prepared in an identical way did not bind to Con A-Sepharose. We conclude that if variants of rat liver GGT exist, they cannot be reliable separated by simple affinity chromatography on Con A-Sepharose of Agarose columns.

Animals↗
PubMed1980

Changes in polysomal polyadenylated RNA and alpha-fetoprotein messenger RNA during hepatocarcinogenesis.

Polysomal polyadenylated RNA was isolated from preneoplastic and neoplastic livers obtained from rats kept on a choline-deficient diet containing ethionine for 8 and 25 to 32 weeks, respectively. Normal, preneoplastic, and neoplastic liver polysomal messenger RNA's (mRNA's) were hybridized with homologous and heterologous 3H-labeled complementary DNA's (cDNA's). The results show that, in terms of RNA mass, all or most of the polysomal polyadenylated RNA present in preneoplastic or neoplastic liver is also present in normal liver. This was induced by the similar extent of hybridization between [3H]cDNA transcribed from preneoplastic or neoplastic liver mRNA's with their homologous mRNA's and with mRNA from normal liver. Conversely, most or all of the polysomal polyadenylated RNA of normal liver is also found in preneoplastic and neoplastic livers, as indicated by the extent of hybridization of [3H]cDNA transcribed from normal liver with mRNA's from normal, preneoplastic, and neoplastic livers. Shifts in the relative abundance of mRNA sequences were detected in the polysomal mRNA of preneoplastic livers and especially in the mRNA of neoplastic liver. Hybridization of alpha-fetoprotein cDNA with liver polyadenylated RNA showed a substantial increase in alpha-fetoprotein mRNA content after 8 and 15 weeks of feeding the carcinogenic diet. Similar experiments using globin cDNA failed to show an increase in globin mRNA content in preneoplastic livers.

Animals↗
PubMed1979

Effects of protein-deprivation on the regeneration of rat liver after partial hepatectomy.

Rats maintained on a protein-free diet for 3 days have an altered time course of hepatic DNA synthesis during liver regeneration. The delay in DNA synthesis is eliminated by the administration of casein hydrolysate (given as late as 6h after partial hepatectomy), but not by glucose or incomplete amino acid mixtures. Despite the change in the timing of DNA synthesis, the increases in hepatic amino acid pools, which take place at the earliest stages of the regenerative process, occur in a normal pattern in the regenerating liver of rats fed the protein-free diet. Protein-deprived rats have increased protein synthesis and decreased rates of protein degradation in the liver in response to partial hepatectomy, but these adaptations do not prevent a lag in protein accumulation and low protein/RNA ratios. The regenerating livers of these animals show a deficit in the accumulation of cytoplasmic polyadenylated mRNA as well as a smaller proportion of free polyribosomes. It is suggested that the deficit in free polyribosomes found in the regenerating liver of protein-deprived rats might be a consequence of the slow accumulation of mRNA species coding for intracellular proteins.

Amino Acids↗
PubMed1979

Accumulation of polyadenylated mRNA during liver regeneration.

Cytoplasmic and polysomal polyadenylated mRNA [poly(A)+-mRNA] increased by 120% prior to the onset of DNA synthesis during the regeneration of rat liver following partial hepatectomy. Despite this large change in cytoplasmic mRNA and an approximately 50% increase in total nuclear RNA, the amount of polyadenylated nuclear RNA increased by only 15--20% during this time. Neither the average size of nuclear or of cytoplasmic polyadenylated mRNA nor the length of their poly(adenylic acid) [poly(A)] tracts changed during liver regeneration. Polysomal poly-(A)+-mRNA increased proportionately more and at a faster rate than rRNA during the first day following partial hepatectomy. Normal livers contained a substantial proportion of cytoplasmic poly(A)+-mRNA not associated with polysomes but this proportion was not altered in 3-h regenerating liver. Thus, in regenerating liver, most preexisting cytoplasmic mRNA does not appear to be recruited into polysomes prior to the substantial increase in the amount of cytoplasmic poly(A)+-mRNA.

Animals↗
PubMed1978

Transcription of the non-repetitive genome in liver hypertrophy and the homology between nuclear RNA of normal and 12 H-regenerating liver.

The percentage of the non-repetitive genome transcribed and the complexity of nuclear RNA were estimated in normal and 12 h-regenerating rat liver. Nuclear RNA from normal or 12 h-regenerating liver hybridizes with approximately 6.1% of non-repetitive DNA (12.2% of the single-copy genome, assuming assymetric transcription). The estimated complexity of either of these nuclear RNA populations is 7.6 . 10(10) daltons, which is approximately 7 times higher than that calculated for polysomal mRNA. Cross hybridization experiments did not show differences between the nuclear RNA populations of normal and 12 h-regenerating liver. The results indicate that liver hypertropy (without hyperplasia) may be brought about without a large increase in the proportion of the non-repetitive genome transcribed.

Animals↗
PubMed1978

Ornithine decarboxylase activity and the onset of deoxyribonucleic acid synthesis in regenerating liver.

Compared with normally fed animals, rats fed on a low-protein diet for 3 days exhibit a considerable delay in DNA synthesis after partial hepatectomy. In the regenerating livers of these animals (a) the timing of the first peak of ornithine decarboxylase activity is not altered and (b) the second peak of enzyme activity is delayed by a few hours, but polyamine concentrations are similar to those of normally fed rats. The results suggest that regardless of the possible effect of polyamines on DNA synthesis, the time course of ornithine decarboxylase activity appears to be independent of the onset of DNA replication in regenerating livers.

Animals↗
PubMed1977

Analysis of gene expression in regenerating rat liver by hybridization of nuclear and cytoplasmic RNA with DNA.

To determine whether massive gene activation occurs in rat liver following partial hepatectomy, DNA-RNA hybridization-saturation and RNA depletion experiments were performed. RNA was extracted from whole cells, nuclei, post-mitochondrial extracts, and polysomes obtained from livers of normal, sham-operated, and partially hepatectomized rats. The purified RNA was labeled with [3H]dimethyl sulfate in vitro and hybridized with nuclera DNA under conditions in which only repetitive sequence transcripts form hybrids with DNA. For comparative purposes, experiments were also performed with nuclear RNA labeled with [32P3phosphoric acid in vivo. The following observations were made: (a) for whole-cell RNA the saturation levels obtained in the hybrization reaction are the same regardless of the source of RNA USED (NORMAL, SHAM-OPERATED, OR PARTIALLY HEPATECTOMIZED RATS); (B) NO DIFFERENCES IN THE SATURATION LEVELS WERE FOUND WHEN LIVER NUCLEAR RNA from these three groups of animals were used; (c) the concentration of nuclear RNA from 6-hr regenerating liver necessary to saturate the DNA is slightly higher than that of nuclear RNA obtained from normal rat liver; (d) cytoplasmic RNA from 6-hr regenerating liver saturates the DNA at a much lower concentration than that required for RNA from normal or sham-operated rats. Our results suggest that for repetitive sequence transcripts, massive "derepression" of the genome does not occur at the early stages of liver regeneration. The alterations detected reflect primarily changes in RNA concentrations rather than qualitative alterations in gene expression. Increased transport of repetitive sequence transcripts from nucleus to cytoplasm appears to take place in regenerating liver.

Animals↗
PubMed1976

Increased collagen synthesis and the kinetic characteristics of prolyl hydroxylase in tissues of rabbits with experimental arteriosclerosis.

Increased aortic and liver prolyl hydroxylase activity has been suggested as an early biochemical indicator of the fibrotic changes which occur in rabbits with injury induced arteriosclerosis. Daily administration of epinephrine (0.025-0.050 mg/kg, i.v.) and thyroxine (0.050 mg/kg, i.p.) to rabbits for 3 weeks produced aortic fibrous plaques with a 4-fold increase in aortic prolyl hydroxylase and also a 5-fold increase in liver prolyl hydroxylase. Histopathologically, the livers of these rabbits show subcapsular areas of necrosis. When total prolyl hydroxylase related antigen was measured. the increase in liver prolyl hydroxylase activity accounted for only a small portion of the total prolyl hydroxylase antigen. However, in the aorta a majority of the increase in antigen is due to the increased amount of enzyme. DNA content per aorta was unchanged and RNA content increased in the aortic tissue of the arteriosclerotic rabbits. However DNA and RNA levels increased 60% in the livers of arteriosclerotic rabbits. In vitro incorporation of radioactively labeled proline into collagenase digestable protein was at least 2-fold greater in aorta and liver minces from arteriosclerotic rabbits. Michaelis--Menten kinetic parameters were obtained for the liver prolyl hydroxylase purified by affinity chromatography from arteriosclerotic rabbits. The Km for the enzyme from treated animals was not significantly different from control. However, the Vmax of the enzyme purified from diseased liver was 4-fold greater when compared to controls.

Animals↗
PubMed1975

Possible interactions between the urea cycle and synthesis of pyrimidines and polyamines in regenerating liver.

Ornithine levels rise progressively in the liver of partially hepatectomized rats, probably as a consequence of the increased flow of metabolites through the urea cycle. Ammonia and urea concentrations in the blood and liber of partially hepatectomized animals are not significantly different from those of sham-operated rats. However, in regenerating livers, the ability to remove ammonia from the blood is close to its maximal limit. Ammonia overload leads to the production of large amounts of orotic acid and causes a marked elevation of hepatic ornithine decarboxylase activity. Among the pyrimidine precursors dihydroorotic acid injections increase the activity of the enzyme while orotic acid is without effect. A peak of labeled material that corresponds to dihydroorotic acid was identified by partition chromatography of acid-soluble extracts of livers of partially hepatectomized rats previously given injections of [14-C2 bicarbonate. The labeling of dihydroorotic acid from [14-C] bicarbibate is increased in the liver of rats given injections of ornithine. Despite the difficulties involved in studies of ornithine decarbozylase activity in vivo, our results suggest that mutual interactions between urea, pyrimidine, and polyamine synthesis take place during liver regeneration.

Adrenalectomy↗