References of "Kremers, Pierre"
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See detailMitogen-Activated Lymphocytes: A Good Model for Characterising Lung Cyp1a1 Inducibility
Lambert, Vincent ULg; Todaro, Anna ULg; Kremers, Pierre ULg et al

in European Journal of Epidemiology (1997), 13(2), 177-83

The CYP1A1 hyperinducibility phenotype occurring in some 10% of the human population corresponds to a higher risk of developing lung cancer. This study was undertaken to assess whether the inducibility ... [more ▼]

The CYP1A1 hyperinducibility phenotype occurring in some 10% of the human population corresponds to a higher risk of developing lung cancer. This study was undertaken to assess whether the inducibility factor, generally evaluated on mitogen-activated lymphocytes after PAH induction, represents correctly the lung situation. Optimal experimental conditions were determined for evaluating, on both lymphocytes and lung tissue explants, the inducibility factor, defined as the ratio of EROD activity (CYP1A1-specific) to cytochrome c reductase activity (unaffected by PAH induction). Paired results for lymphocytes and lung tissue samples from 10 lung cancer patients were compared. A good correlation was observed between lymphocyte and lung tissue inducibilities (R = 0.809; p = 0.005). In conclusion, mitogen-activated lymphocyte inducibility is indicative of lung tissue inducibility and constitutes a good marker for evaluating individual PAH inducibilities. [less ▲]

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See detailHierarchical Cluster Analysis of Environmental Pollutants through P450 Induction in Cultured Hepatic Cells
Dubois, Marilyn; Plaisance, H.; Thomé, Jean-Pierre ULg et al

in Ecotoxicology & Environmental Safety (1996), 34(3), 205-15

Environmental pollutants are classically associated with increased drug metabolism. Cultures of rat hepatocytes, quail hepatocytes, and human hepatoma (Hep G2) cells were used to study the effects of ... [more ▼]

Environmental pollutants are classically associated with increased drug metabolism. Cultures of rat hepatocytes, quail hepatocytes, and human hepatoma (Hep G2) cells were used to study the effects of pesticides on drug-metabolizing enzymes. Membrane integrity and mitochondrial activity were evaluated and induction of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities were measured. Induced P450s were identified by immunoblotting. Pentachlorophenol and lindane appeared as the strongest inducers. On the immunoblots, specific antibodies revealed induced CYP1A1 in fetal rat hepatocytes, CYP2B in quail hepatocytes, and CYP3A7 in Hep G2 cells. Pesticide effects on these different activities in each type of cultured cells were compared by cluster analysis. Results obtained under similar conditions with reference inducers phenobarbital (PB) and benzo[a]anthracene and other environmental pollutants (polychlorobiphenyls) were added to previous data prior to multivariate analysis. The tested products fell into four major groups: a first group with pentachlorophenol, identified as a CYP3A inducer; a second group containing the methylcholanthrene-type inducers that increase CYP1A-related activities; a third class represented by dieldrin, a PB-type inducer; a fourth group including inert compounds or weak inducers. Lindane shares the criteria of the second and third groups and seems to induce both CYP1A and CYP2B activities. The current study results highlight the advantage of using several types of cultured hepatocytes to evaluate the short-term toxicity of environmental pollutants in vitro and constitute a useful model for predicting the potential toxicity of pesticides in humans (Hep G2 cells) and wildlife (fetal quail hepatocytes). [less ▲]

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See detailUltrastructural Modifications in Cultured Fetal Quail Hepatocytes Exposed to Pesticides and Pcbs
Hugla, J. L.; Goffinet, Gerhard ULg; Kremers, Pierre ULg et al

in Ecotoxicology & Environmental Safety (1996), 34(2), 145-55

There is increasing interest in cultured hepatocytes as a tool for solving toxicological and pharmacological problems while reducing laboratory animal experimentation. In the present study, fetal ... [more ▼]

There is increasing interest in cultured hepatocytes as a tool for solving toxicological and pharmacological problems while reducing laboratory animal experimentation. In the present study, fetal hepatocytes from the Japanese quail (Coturnix coturnix japonica) were used as an in vitro alternative model for evaluating the effects of PCBs and various pesticide-type chemicals on cell ultrastructure. Major alterations were demonstrated. The most striking effects of toxicants were an increase in the number of cisternae of the rough endoplasmic reticulum (RER), various alterations of mitochondrial morphology, a decreased glycogen content, vacuolization of the cytoplasm, and the appearance of concentric membrane arrays (CMA's), also called myelin-like figures. Other changes were sometimes observed, such as altered cell junctions, an increased lipid content, deformations of the nuclei, or the appearance of crystalline structures. These ultrastructural modifications seem to be dose-dependent. The present in vitro findings are validated by similar observations previously made in vivo on Japanese quail. They confirm the effectiveness of this technique as a biomonitoring tool for the evaluation of environmental quality. Yet the multiplicity of possible toxic effects, even for xenobiotics of a same category, makes it necessary to screen additional indicators of toxicity, such as the detoxifying activity of monooxygenases. [less ▲]

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See detailEffects on Pcbs on Liver Ultrastructure and Monooxygenase Activities in Japanese Quail
Stouvenakers, Nadine ULg; Hugla, J. L.; Goffinet, Gerhard ULg et al

in Bulletin of Environmental Contamination & Toxicology (1996), 56(5), 839-46

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See detailEffect of Inducers and Pcbs on the Cytochrome P450 Enzymes in Cultured Quail Hepatocytes
Roelandt, L.; Dubois, Maryline; Todaro, Anna ULg et al

in Ecotoxicology & Environmental Safety (1995), 31(2), 158-63

Hepatocytes isolated from fetal quail livers (Coturnix coturnix japonica) were cultured in vitro. Their capacity to metabolize drugs and xenobiotics was explored with typical cytochrome P450 substrates ... [more ▼]

Hepatocytes isolated from fetal quail livers (Coturnix coturnix japonica) were cultured in vitro. Their capacity to metabolize drugs and xenobiotics was explored with typical cytochrome P450 substrates: ethoxycoumarin (known to be metabolized by several P450s), ethoxyresorufin (essentially dealkylated by P450IA1), and testosterone (specifically hydroxylated at several positions by several P450s). The cells could be kept metabolically active in culture for at least 4 days. Their drug-metabolizing activities were inducible by the usual P450 inducers, like phenobarbital and benzanthracene, but also by Aroclor 1254, a PCB mixture. The results obtained indicate that this experimental model could certainly be very helpful in ecotoxicological studies. [less ▲]

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See detailEffects of Pcbs (Aroclor 1254) on Cytochrome-P450 Expression and Monooxygenase Activities in Cultured Foetal Rat Hepatocytes
Roelandt, L.; Todaro, Anna ULg; Thomé, Jean-Pierre ULg et al

in Toxicology (1995), 98(1-3), 95-103

Polychlorinated biphenyls (PCBs) are widespread residual micropollutants which accumulate in living organisms, probably as a consequence of their high lipophilicity. Cultured foetal rat hepatocytes used ... [more ▼]

Polychlorinated biphenyls (PCBs) are widespread residual micropollutants which accumulate in living organisms, probably as a consequence of their high lipophilicity. Cultured foetal rat hepatocytes used as target cells constitute an interesting in vitro model for studying the mechanisms of action of PCBs. In this paper, and the accompanying one (Toxicology 98 (1995) 83-94), we have used this model to investigate the effects of PCBs on several cellular parameters. The inducibility of CYPIA1 is the most sensitive parameter studied, as shown by the induction of ethoxycoumarin-O-deethylase and ethoxyresorufin-O-deethylase activities at PCB concentrations as low as 1 microM. Dexamethasone treatment of the cells potentiates this induction. PCB induction is reversible and occurs even in cells cultured for several days. CYP2B and CYP3A seem unaffected by PCBs in this experimental system. By inducing CYP1A1, PCBs can trigger the 'activation' of xenobiotics, such as polycyclic hydrocarbons, into mutagenic compounds. [less ▲]

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See detailCytotoxic Effects of Aroclor 1254 on Ultrastructure and Biochemical Parameters in Cultured Foetal Rat Hepatocytes
Thomé, Jean-Pierre ULg; Roelandt, L.; Goffinet, Gerhard ULg et al

in Toxicology (1995), 98(1-3), 83-94

The cytotoxicity of a commercial PCB mixture, Aroclor 1254, was assessed on cultured foetal rat hepatocytes. Under control conditions, dexamethasone stimulates immature hepatocytes to differentiate into ... [more ▼]

The cytotoxicity of a commercial PCB mixture, Aroclor 1254, was assessed on cultured foetal rat hepatocytes. Under control conditions, dexamethasone stimulates immature hepatocytes to differentiate into both hepatocytes and biliary epithelial cells. Consequently, foetal rat hepatocytes maintain, in vitro, a liver-like organization with spaces corresponding to the lumen of biliary canalicules, many mitochondria, and a well-developed rough endoplasmic reticulum (RER). This in vivo-like organization of cultured rat hepatocytes remains unchanged in medium supplemented with Aroclor 1254 at concentrations below 25 microM. In the 25-125 microM concentration range, however, PCBs severely alter some cellular organelles, notably causing important development of the RER and the appearance of cytoplasmic lacunae containing laminated concentric membrane arrays. In addition, the number of lipid droplets increases, the glycogen islets disappear, and dramatic local alterations of the mitochondrial cristae occur. In exposed and unexposed cells, the following biochemical parameters were measured: the DNA content, protein synthesis, lipid peroxidation, and urea formation. The results show that Aroclor 1254 at concentrations exceeding 25 microM (but not at lower concentrations) causes irreversible damage to cultured hepatocytes. The observed ultrastructural modifications are in good agreement with several in vivo studies on rat liver. Thus, isolated foetal rat hepatocytes have considerable potential as an alternative to whole animals for use in (eco)toxicological studies. [less ▲]

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See detailExpression and Induction of Drug-Metabolizing Enzymes in Cultured Fetal Rat Hepatocytes
Kremers, Pierre ULg; Roelandt, L.; Stouvenakers, Nadine ULg et al

in Cell Biology and Toxicology (1994), 10(2), 117-25

An in vitro experimental model, fetal rat hepatocytes in culture, was metabolically characterized. Several enzymatic activities were expressed in these hepatocytes, namely, testosterone hydroxylations ... [more ▼]

An in vitro experimental model, fetal rat hepatocytes in culture, was metabolically characterized. Several enzymatic activities were expressed in these hepatocytes, namely, testosterone hydroxylations. Hepatocytes cultured up to 3 weeks in the presence of dexamethasone and phenobarbital still expressed some drug-metabolizing enzyme activities (e.g., ECOD). The enzymatic activities were measured both directly on monolayers during culture and on the corresponding harvested and homogenized cells. The results correlate perfectly with each other. The 'on cell' procedure allows us to repeat the assay or to measure several activities on the same cells at different time intervals. The presence of dexamethasone in the culture medium allows the expression and the induction of several cytochrome P450 isoenzymes, namely, those hydroxylating testosterone. This makes the model particularly attractive for induction experiments as well as for metabolic or toxicological studies needing longer treatments. [less ▲]

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See detailGenetic regulation of hepatic steroid 16 alpha-hydroxylase activities in inbred strains of mice.
Pasleau, Françoise ULg; Kolodzici, Claudine; Kremers, Pierre ULg et al

in Endocrinology (1984), 115

Steroid 16 alpha-hydroxylase activities and properties were studied in C57Bl/6J, 129/J, AKR/R, DBA/2J, C3H/I, and BALB/c mouse liver using four different substrates. The highest enzymatic activities were ... [more ▼]

Steroid 16 alpha-hydroxylase activities and properties were studied in C57Bl/6J, 129/J, AKR/R, DBA/2J, C3H/I, and BALB/c mouse liver using four different substrates. The highest enzymatic activities were measured in the female mice, with the exception of the 129/J females. As in the rat liver, the sexual differentiation of the steroid 16 alpha-hydroxylation observed in adult male and female mice took place at puberty. In the adult mouse liver, two steroid 16 alpha-hydroxylase activities (forms I and II) could be differentiated on the basis of their relative affinities for the various steroid substrates and their relative proportions in male and female mouse livers. In the immature mouse liver, no sexual differences could be detected, and the mice of both sexes presented phenotypes identical to those of the adult female. The adult 129/J females appeared genetically deficient with respect to the form I of the steroid 16 alpha-hydroxylase and presented a phenotype identical to that of the adult male mice of the various strains tested. Differences in hydroxylase activities between the C57Bl/6J and 129/J strains were investigated using standard genetic breeding protocols. Steroid 16 alpha-hydroxylase seemed to be inherited additively in the liver of the female mice obtained by crossing the C57Bl/6J male and the 129/J female or the 129/J male and the C57Bl/6J female. In the male mice, regardless of genotype, the observed phenotype was always identical to the two male parental types. Both hormonal and genetic regulations were responsible for the different phenotypes occurring in adult male and female C57Bl/6J and 129/J mouse livers. [less ▲]

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See detailGenetic regulation of hepatic steroid 16alpha-hydroxylase activities in inbred strains of mice.
Pasleau, Françoise ULg; Kolodzici, Claudine; Kremers, Pierre ULg et al

Poster (1982, September)

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See detailOntogenic development of steroid 16 alpha-hydroxylase as a tool for the study of the multiplicity of cytochrome P-450.
Pasleau, Françoise ULg; Kolodzici, Claudine; Kremers, Pierre ULg et al

in European Journal of Biochemistry (1981), 120

1. Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16 alpha-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the four enzymic activities ... [more ▼]

1. Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16 alpha-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the four enzymic activities increase in parallel to the concentration of cytochrome P-450. Until puberty, they develop similarly in male and female rat livers. From the 40th to the 55th day, the four steroid 16 alpha-hydroxylase activities increase rapidly in the male rat liver. The sexual differentiation of the steroid 16 alpha-hydroxylation observed in adult male and female rats takes place around the 55th day. 2. In the adult rat liver, steroid 16 alpha-hydroxylase is supported by two forms of cytochrome P-450 (form I and form II), which differ in their relative affinities for the various steroid substrates, and by their relative proportions in male and female rat livers. These two forms of cytochrome P-450 are also present in the young male and female rat livers, but are roughly equal in proportion. The transition from the immature to the adult repartition of the two forms occurs during puberty and is correlated with the sexual differentiation of the steroid 16 alpha-hydroxylase activities. 3. During the critical phases of the rat ontogenic development, the in vitro interactions between benzo[a]pyrene and steroids were compared at the level of two rat liver monooxygenases: steroid 16 alpha-hydroxylase and aryl hydrocarbon hydroxylase. (a) In the immature male and female rat livers, progesterone 16 alpha-hydroxylase, and to a lesser extent, pregnenolone 16 alpha-hydroxylase are inhibited by benzo[a]pyrene. Progesterone 16 alpha-hydroxylase is also inhibited by metyrapone. (b) In the young rat, aryl hydrocarbon hydroxylase cannot be inhibited by steroids and appears to be supported by a single form of cytochrome P-450. The transition from the immature to the adult situation occurs around the 40th day. [less ▲]

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See detailCompetition between benzo[a]pyrene and various steroids for cytochrome P-450-dependent rat liver monooxygenases.
Pasleau, Françoise ULg; Kremers, Pierre ULg; Gielen, Jacques

in Chemico-Biological Interactions (1981), 34

Cytochrome P-450-dependent monooxygenases are able to oxidize a large variety of endogenous and exogenous substrates. This paper describes the in vitro interaction between benzopyrene and steroids at the ... [more ▼]

Cytochrome P-450-dependent monooxygenases are able to oxidize a large variety of endogenous and exogenous substrates. This paper describes the in vitro interaction between benzopyrene and steroids at the level of two rat liver monooxygenases: steroid-16 alpha-hydroxylase and aryl hydrocarbon hydroxylase (AHH). The results obtained suggest the following conclusions: (1) Steroid-16 alpha-hydroxylase is partially supported by a specific cytochrome P-450 form which is not inhibited in vitro by exogenous substrates. Steroid-16 alpha-hydroxylase is completely independent from cytochrome P1-450 (or P-448), as it is insensitive, in vitro, to alpha-naphthoflavone; (2) AHH is supported by two cytochrome P-450 forms: a specific form which is inducible by methylcholanthrene and inhibited in vitro by alpha-naphthoflavone, but is insensitive to metyrapone and steroids; and another less specific form which is inhibited by metyrapone and steroids in vitro. [less ▲]

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See detailSex differences in the activity of different cytochrome P450 dependent steroid 16alpha-hydroxylases in rat liver
Pasleau, Françoise ULg; Kremers, Pierre ULg; Gielen, Jacques

in Journal of Steroid Biochemistry & Molecular Biology (1980), 13

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See detailBiochemical and biological properties of steroid 16alpha-hydroxylase.
Gielen, Jacques; Cantineau, Robert; Degraeve, Jacques et al

Conference (1980, March)

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See detailSteroid 16alpha-hydroxylase multiplicity in rat liver.
Gielen, Jacques; Kremers, Pierre ULg; Pasleau, Françoise ULg

in Biochemistry, Biophysics and Regulation of Cytochrome. (1980)

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See detailRégulation de l’activité des monooxygénases microsomales au cours de la croissance.
Gielen, Jacques; Kremers, Pierre ULg; Pasleau, Françoise ULg

in Les Colloques de l'INSERM, Pharmacologie du Développement (1979)

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See detailIs steroid 16alpha-hydroxylase supported by more than one mono-oxygenase.
Kremers, Pierre ULg; Pasleau, Françoise ULg; Gielen, Jacques

in Biochemical and Biophysical Research Communications (1978)

Steroid-16α-hydroxylase activities have been measured in normal and induced rat livers using four different substrates. The male/female activity ratio as well as the induction factor vary with the ... [more ▼]

Steroid-16α-hydroxylase activities have been measured in normal and induced rat livers using four different substrates. The male/female activity ratio as well as the induction factor vary with the substrate indicating that steroid-16α-hydroxylase activity is a heterogenous enzyme. Experiments using specific inhibitors led to the conclusion that steroid-16α-hydroxylase is supported by at least two cytochrome P-450 forms, different from the cytochrome P-448. [less ▲]

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See detailMultiplicity of cytochrome P450 dependent steroid 16alpha-hydroxylase in the rat liver.
Kremers, Pierre ULg; Pasleau, Françoise ULg; Gielen, Jacques

Conference (1978, June)

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