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Biomedical subjects

H Sidransky

Publications and source records attributed to H Sidransky.

At least 73 records · Page 4Linked to original sources
PubMed1979

Effect of inhibitory and stimulatory agents on protein synthesis in hepatomas and host livers of rats.

Female inbred BUF rats bearing intrahepatically transplanted hepatomas (5123 or 19) were subjected to acute exposure to a variety of hepatotoxic agents (actinomycin D, aflatoxin B1, CCl4, dimethylnitrosamine, ethionine, puromycin, or sparsomycin) or of stimulatory agents (hydrocortisone, phenobarbital, or whole-body X-ray). The responses in terms of changes in polyribosomes and protein synthesis (in vitro and in vivo) of host liver and hepatoma were evaluated. The responses of the host livers and hepatomas to the different agents varied. In general, the host livers responded much more than did the hepatomas. Of the two hepatomas, hepatoma 19 responded less (particularly in terms of polyribosome changes) than did hepatoma 5123. In a few experiments, different doses of actinomycin D, ethionine, or sparsomycin were used and in all instances the host livers responded more than did the hepatomas.

Animals↗
PubMed1979

Stability of messenger ribonucleic acid of free and membrane-bound polyribosomes of the livers of rats treated with ethionine.

Administration of ethionine to female rats results in disaggregation of free and membrane-bound polyribosomes and inhibition of protein synthesis in the liver. The administration of adenine and methionine to ethionine-treated rats reverses these effects, even after actinomycin D treatment which inhibits new RNA synthesis. The membrane-bound polyribosomes show greater recovery of the state of aggregation and of in vitro protein synthesis than do the free polyribosomes of rat liver. The messenger RNA (mRNA) in the recovering membrane-bound polyribosomes appears to come from endoplasmic reticulum membranes and is not related to increased nucleocytoplasmic translocation of existing mRNA. Initiation factors-dependent stimulation of polyphenylalanine synthesis by ribosomes and by initiation factors of membrane-bound polyribosomes is increased more than the synthesis by ribosomes and by initiation factors of free polyribosomes in the livers of ethionine-treated rats receiving actinomycin D and adenine plus methionine. Our results suggest that stable mRNA associated with membranes remains in the rat liver after injury by ethionine, and during recovery induced by adenine and methionine, the mRNA is utilized to reform membrane-bound polyribosomes.

Adenine↗
PubMed1978

Age-related changes in ribosomal profiles and in vitro protein synthesis in skeletal muscle during fasting and subsequent refeeding of rats.

Age-dependent changes in ribosomal profiles and in in vitro protein synthesis in skeletal muscle (gastrocnemius muscle) were studied in rats subjected to fasting and subsequent refeeding. Male rats of 4, 7, and 21 weeks of age were used. Incorporation of 14C-leucine into protein in vitro using skeletal muscle ribosomes from fed rats decreased with the age of the animals. Sucrose density gradient analyses of ribosomal profiles revealed that the changes in protein synthesis were accompanied by progressive declines in the concentrations of polyribosomes and total RNA in skeletal muscle. After fasting for 1 or 2 days, protein synthesis in muscle of young rats dropped markedly and this change could be attributed to the fall in the concentrations of polyribosomes. Also, the concentration and total RNA in the muscles of the young rats decreased. During refeeding of rats after fasting for 2 days, the incorporation of 14C-amino acids into protein recovered more efficiently using ribosomes of skeletal muscle of young animals compared with using those of older animals. This rapid increase in the protein synthesizing activity of skeletal muscle may be related to the efficient recovery of the ribosomes toward heavier aggregates. The results indicate that young animals adapt more efficiently to fasting and refeeding than do older animals.

Aging↗
PubMed1978

Turnover of messenger RNA in transplantable hepatomas and host liver of rats.

The turnover of messenger RNA (mRNA) in two intrahepatically transplantable hepatoma (5123 and 19) and host livers of Buffalo rats was evaluated with four different approaches. [14C]Orotic acid incorporation into the rapidly labeled peak between 18S and 4S of total polyribosomal RNA was measured. In vitro RNase assay of [14C]orotic acid-labeled mRNA of polyribosomes was utilized. The decay of mRNA as reflected by disaggregation of free and membrane-bound polyribosomes at intervals after actinomycin D treatment was determined. The incorporation of [14C]orotic acid into polyadenylic acid-mRNA of free and membrane-bound polyribosomes was assayed. The results revealed that the turnover of mRNA of total, free, and membrane-bound polyribosomes was greater in the host livers than it was in the two hepatomas. In host livers the turnover of mRNA of the free polyribosomes was greater than that of the membrane-bound polyribosomes. In the two hepatomas the turnover of mRNA of free polyribosomes was at a similar rate as that of membrane bound polyribosomes. Hepatoma 19, which grow more rapidly and is less differentiated morphologically than is hepatoma 5123, appeared to have a slower turnover of mRNA than did hepatoma 5123. Measurement of RNase activity revealed greater activity in host livers than in hepatomas.

Animals↗
PubMed1977

The effect of tryptrophan on nucleocytoplasmic translocation of RNA in rat liver.

The effect of the administration of tryptophan on the transport of nuclear poly (A)-containing mRNA to the cytoplasm in rat liver was investigated. Administration of tryptophan to fasted rats pretreated with cordycepin and actinomycin D led to decreased levels of nuclear poly (A)-mRNA and a concomitant increase in the levels of polyribosomal poly (A)-mRNA in the cytoplasm as determined by measuring in vivo incorporation of labeled precursors into hepatic RNA. Using isolated hepatic nuclei of rats prelabeled in vivo with [14C]orotic acid, there was greater release of labeled poly(A)-mRNA into the incubation medium from nuclei of tryptophan-treated rats than from nuclei of control animals. The increased release of RNA from hepatic nuclei of tryptophan-treated animals was not related to the cell sap present in the media since cell saps from livers of control and experimental rats gave similar results. These results support earlier findings which suggest that in the rat tryptophan increases the rate of translocation of hepatic poly(A)-mRNA from nucleus to cytoplasm.

Animals↗
PubMed1977

Effect of aflatoxin B1 on hepatic polyribosomes and protein synthesis in the rat.

This study was concerned with the effect of aflatoxin B1 on protein synthesis in rat liver. Specifically, the effect of the administration of aflatoxin B1 (6.0 mg/kg body weight) on hepatic polyribosomes (free and membranebound), protein synthesis in vitro, and initiation factors activity of rats within 3-12 h was investigated. The results revealed that aflatoxin B1 rapidly led to disaggregation of free and membrane-bound polyribosomes, to inhibition of in vitro protein synthesis by both populations of polyribosomes, to little or no effect on the activities of initiation factors, and to defective ribosomes, particularly the 60S ribosomal subnits, of both types of polyribosomes. Comparative studies on the effects of aflatoxin B1 and actinomycin D revealed progressive disaggregation by both hepatic free and membrane-bound polyribosomes after aflatoxin B1 but not only of the free polyribosomes after actinomycin D.

Aflatoxins↗
PubMed1977

Effect of tryptophan or phenobarbital administration on hepatic polyribosomes and protein synthesis in rats force-fed a complete or threonine-devoid diet.

Young rats were force-fed a complete or threonine-devoid diet for 3 days. Prior to killing on the fourth morning rats of each group were treated with l-tryptophan (30 mg/100 g body weight) 2 hours before killing or with sodium phenobarbital (8 mg/100 g body weight) 14 hours before killing. Rats force-fed the threonine-devoid diet revealed increased aggregation of polyribosomes (sucrose density gradient analyses) and increased protein synthesis (in vitro [14C]leucine incorporation into protein) in the livers in comparison to that in the livers of rats force-fed the complete diet. Plasma total tryptophan levels were decreased and plasma free tryptophan as a percentage of total plasma tryptophan was increased in rats force-fed the threonine-devoid diet for 3 days. Administration of tryptophan or of phenobarbital stimulated polyribosomal aggregation and in vitro protein synthesis of the livers of rats force-fed the complete or the threonine-devoid diet. These stimulatory effects incuded by tryptophan or phenobarbital were most marked in rats force-fed the threonine-devoid diet. Hepatic tryptophan pyrrolase activity was stimulated to similar degrees following the administration of tryptophan to rats force-fed the complete or the threonine-devoid diet.

Animals↗
PubMed1976

The effect of cycloheximide on hepatic RNA synthesis and nucleolar size in rats force-fed a threonine-devoid diet.

Young rats were force-fed a complete or threonine-devoid diet for 3 days. On the fourth morning, rats of each group were injected intraperitoneally with cycloheximide (150 mug/100 g body weight) or saline with [6-14C]orotic acid 30 minutes later, 2 hours before killing. Incorporation of [6-14C]orotic acid into hepatic RNA fractions (whole homogenate, postmitochondrial supernatant, microsomes, ribosomes, nuclei and soluble) revealed elevated levels (cpm/mg RNA) in rats force-fed the threoninedevoid diet in comparison to those of rats force-fed the complete diet. However, treatment with cycloheximide decreased the incroporation of [6-14C]orotic acid into the hepatic RNA fractions of the rats force-fed the threonine-devoid diet to levels that were similar to those in rats force-fed the complete diet with or without cycloheximide treatment. Studies dealing with nucleoli isolated by sucrose gradients from livers of control and experimental rats revealed heavier nucleoli and more radioactive labeled RNA in nucleoli ([6-14C]orotic acid administered 30 minutes before killing) of rats force-fed the threonine-devoid diet than in those force-fed the complete diet for 3 days. Treatment with cycloheximide decreased the elevated incorporation in the experimental rats. Also, electron microscopic studies revealed that after cycloheximide treatment, the enlarged hepatic nucleoli of the experimental rats became smaller and returned to a more normal pattern, as found in the control rats. The studies suggest that active hepatic protein synthesis is involved in the increased hepatic RNA synthesis in rats force-fed the threonine-devoid diet and that following inhibition of protein synthesis, as induced by cycloheximide, there is a rapid inhibition of the accelerated hepatic RNA synthesis observed in rats force-fed the threonine-devoid diet with a rapid reversal toward a normal level, i.e. toward that found in control rats.

Animals↗