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L Corcos

Publications and source records attributed to L Corcos.

17 recordsLinked to original sources
PubMed1990

Effect of phenobarbital on the glucocorticoid receptor in rat hepatoma cells.

Phenobarbital is a potent inducer of several liver-specific genes such as those encoding detoxication enzymes, including cytochromes P450. However, the mechanisms of action of the barbiturate are poorly understood. Since both, phenobarbital and glucocorticoids, are capable of inducing the same cytochrome P450 species, we asked whether the glucocorticoid receptor could participate to the phenobarbital induced responses. The results presented here show that phenobarbital was able to induce a two-fold increase in the affinity of the glucocorticoid receptor for the binding of dexamethasone, as well as a 30% increase of the receptor number in Reuber rat hepatoma cells of the Fao line. These effects may have a biological significance since they were paralleled by an enhancement of the dexamethasone-induced tyrosine aminotransferase activity, a glucocorticoid inducible function in rat hepatoma cells and in rat liver. To our knowledge, phenobarbital is the first compound shown to be able to induce, in intact cells, an increase in the affinity of the glucocorticoid receptor for the binding of its ligand.

Animals↗
PubMed1990

Genetic analysis of aflatoxin B1 activation in rat hepatoma cells.

We present a strategy to elucidate the rate-limiting steps in activation of carcinogenic compounds by cytochromes P450. The principle was to select Reuber rat hepatoma cells for resistance to a procarcinogen. The hypothesis was that resistant cells should be systematically deficient in the P450 enzyme(s) involved in the activation process. Here we present an example of the use of this approach using aflatoxin B1 (AFB1), a potent hepatocarcinogen, as the selective agent. Parental cells as well as individual and pooled colonies selected for AFB1 resistance from three independent rat hepatoma lines were characterized for their content of 1) mRNA hybridizing to cDNA and/or oligonucleotide probes for cytochromes P450IIB1, P450IIB2 and albumin; and 2) aldrin epoxidase activity. Parental aflatoxin B1-sensitive cells were shown to express P450IIB1 but not P450IIB2. The majority of the aflatoxin B1-resistant clones failed to accumulate cytochrome P450IIB1 mRNA and expressed no or only very low aldrin epoxidase activity. Albumin mRNA levels remained unchanged, demonstrating that loss of expression of cytochrome P450IIB1 was not a consequence of a general dedifferentiation event. A revertant population showing restoration of both cytochrome P450IIB1 mRNA accumulation and aldrin epoxidase activity was fully sensitive to aflatoxin B1. The correlation between expression of cytochrome P450IIB1 and sensitivity to aflatoxin B1 in both parental cells and revertants strongly suggests that cytochrome P450IIB1 is a major contributor to the activation of aflatoxin B1 in rat hepatoma cells. The kind of strategy described here could be applied to other compounds that become cytotoxic for hepatoma cells following activation by cytochromes P450.

Aflatoxin B1↗
PubMed1989

Establishment of mouse and rat hepatoma cell clones showing stable expression of rabbit cytochrome P450 IA2.

Cytochrome P450 IA2, a liver-specific member of the 3-methylcholanthrene-inducible family, is never detected in established cell lines. With the aim of isolating cells stably producing this protein, we have used rat and mouse hepatoma cells as recipients in transfection experiments involving rabbit cytochrome P450 IA2 cDNA. We report here the isolation of five hepatoma cell clones expressing functional P450 IA2. The level of expression is comparable to that found in COS cells transiently transformed by other P450 cDNAs. It ranges between 0.4 and 1.6 pmol P450 IA2/mg total cell protein.

Animals↗
PubMed1988

Phenobarbital, dexamethasone and benzanthracene induce several cytochrome P450 mRNAs in rat hepatoma cells.

Hepatoma cells derived from the Reuber H35 rat hepatoma express cytochrome P450 enzymes of two major families: polycyclic aromatic hydrocarbon-inducible forms are found in both differentiated and dedifferentiated cells while phenobarbital (PB)-inducible forms are found only in differentiated cells. We report here that (i) benzanthracene and PB induce P450 c mRNA in differentiated and dedifferentiated cells and (ii) dexamethasone and PB induce P450 b/e and/or P450 PB1 mRNAs in differentiated cells but not in dedifferentiated cells.

Animals↗
PubMed1988

Efficient one-step selection of hepatoma cell variants of a variety of phenotypes by use of aflatoxin B1.

We have developed a method to select for rat hepatoma cells that fail to express hepatocyte-specific functions. Well-differentiated cells descended from the H4IIEC3 hepatoma line express aldrin epoxidase (AE) activity, an indicator of the liver-specific forms of cytochromes P450 and, concurrently, are able to activate the procarcinogen aflatoxin B1 (AFB1) into highly toxic metabolites. Thus, differentiated hepatoma cells are highly sensitive to AFB1, while dedifferentiated derivatives, which fail to express AE activity, are resistant. Exposure of differentiated Fao cells to 10 microM AFB1 for 24 h permits the isolation, at a frequency of 5 x 10(-5), of resistant colonies that exhibit strongly reduced AE activity. Strikingly, various morphological types can be observed. In more than 90% of the colonies, cells are morphologically similar to the original differentiated cells and accumulate all liver-specific mRNAs examined in amounts comparable to Fao cells. Moreover, they are able to carry out gluconeogenesis, as judged by their capacity to grow in glucose-free medium. For a minor fraction of colonies, the cells exhibit nonhepatic morphology. These cells fail to express three or more of the liver functions and are not able to proliferate in glucose-free medium. Our results demonstrate that the use of AFB1 constitutes a simple and efficient single-step selective method for obtaining variant hepatoma cells of a wide variety of phenotypes.

Aflatoxin B1↗
PubMed1985

Expression of the mouse serum albumin gene introduced into differentiated and dedifferentiated rat hepatoma cells.

A 23-kilobase-pair segment of DNA containing the entire mouse serum albumin gene as well as 2.2 kilobase pairs of 5' and 4.3 kilobase pairs of 3' flanking sequences has been introduced into pSV2dhfr, a plasmid in which expression of the mouse dihydrofolate reductase cDNA is under the control of simian virus 40 sequences. This vector, pSV2dhfr-alb, was used to transfect differentiated and variant dedifferentiated rat hepatoma cells. Nine independent clones of transfected differentiated cells secrete considerable amounts of mouse albumin, while the expression of the normal rat albumin is the same as in nontransfected cells. In contrast, only small amounts of mouse and rat albumin are produced by transfected dedifferentiated cells. The amounts of albumin mRNA present in the cells are consistent with the amounts of albumin produced. These results show that a transfected gene can be regulated in a fashion consistent with the overall differentiation profile of the cell.

Animals↗
PubMedDate not supplied

Phenobarbital and dexamethasone induce expression of cytochrome P-450 genes from subfamilies IIB, IIC, and IIIA in mouse liver.

Phenobarbital (PB) and dexamethasone (DEX) induce several liver-specific cytochrome P-450 mRNAs in rats. We examined the induction of P-450 mRNAs from families IIB, IIC, and IIIA by PB and DEX in six inbred mouse strains. P-450IIB1-related mRNA species were induced 3- to 13-fold by PB and 3- to 15-fold by DEX in all animals. P-450IIC6-related mRNA species were induced 3- to 7-fold by PB in males and females, and up to 5-fold by DEX in most males but not in female mice, in which DEX was inactive. P-450IIIA-related mRNA species were induced 2- to 7-fold by PB and 2- to 20-fold by DEX in all animals of either sex. In DBA/2J female mice, both inducers triggered a comparable early response (4 hr) at a low dose (10 mg/kg) for all three gene subfamilies, the maximum being reached between 8 and 18 hr of treatment with 100 mg/kg. Under the optimal induction conditions, coadministration of PB and DEX did not lead to any further increase in the responses. These results demonstrate the existence of analogies, as well as striking differences in the inductive effects of PB and DEX between rats and mice. They also indicate the possible involvement of these inducers in related inductive pathways for three cytochrome P-450 gene subfamilies in mouse liver.

Animals↗
PubMedDate not supplied

[External valvuloplasty of the sapheno-femoral junction].

Authors describe the pathophysiologic premises, technique and results obtained, in over two years, in N. 40 external valvuloplasties of the sapheno-femoral junction, performed with the following main indications: sapheno-femoral reflux and U.S. evidence of normal valve leaflets in the terminal valves of the long saphenous vein. Dilatation of the terminal segment of the long saphenous vein is reduced with the application of an external synthetic prosthesis and valvular function is restored. Good results have been obtained in N. 35 cases (87.5%). A careful pre- and peroperative procedure is necessary in order to avoid failures.

Blood Vessel Prosthesis↗
PubMedDate not supplied

[Peripheral venous biopsy in the selection of autologous venous grafts].

Authors explain their experiences on the study and further clinical application of peripheral venous biopsy (dorsal food vein) as a systematic diagnose method for phlebopatic patients. Results from these experience seem to support the availability of this method to select patients candidates for an autologous venous graft in Cardiovascular Surgery. Peripheral venous biopsy, such as for the dorsal food vein, allows to individualize the possible injuries at the saphenous wall, previously its use for autologous graft; and it avoids the preliminary sample taking for biopsy. By this method, the requirement of an intraoperatory biopsy is also avoided and an eventual by-pass or substitution are better programmed.

Biopsy↗