Burnout syndrome among undergraduate nursing students at a public university / Síndrome de Burnout entre estudantes de graduação em enfermagem de uma universidade pública / Síndrome de Burnout entre estudiantes de pregrado en enfermería de una universidad pública

OBJECTIVE: to investigate the burnout syndrome and its relationship with demographic and academic variables among undergraduate nursing students at a public university in Southern Brazil. METHOD: a quantitative study with 168 students, by applying an adaptation of the Maslach Burnout Inventory - Student Survey, validated for this study. We used descriptive and variance analysis of the data analysis. RESULTS: we found that students do not have the burnout syndrome, manifesting high average scores in Emotional Exhaustion, low in Disbelief and high in Professional Effectiveness; that younger students who perform leisure activities have greater Professional Effectiveness, unlike students in early grades with no extracurricular activities; combining work and studies negatively influenced only the Professional Effectiveness factor, while the intention of giving up influenced negatively Disbelief and Professional Effectiveness factors. CONCLUSION: the situations that lead students to Emotional Exhaustion need to be recognized, considering the specificity of their study environments. .

OBJETIVO: investigar a síndrome de Burnout e sua relação com variáveis sociodemográficas e acadêmicas, entre estudantes de graduação em enfermagem de uma universidade pública do Sul do Brasil. MÉTODO: estudo quantitativo, realizado com 168 estudantes, mediante a aplicação de uma adaptação do Maslach Burnout Inventory - Student Survey, validada para este estudo. Utilizou-se a análise descritiva e de variância para análise dos dados. RESULTADOS: constatou-se que os estudantes não apresentam a síndrome de Burnout, manifestando médias altas em exaustão emocional, baixas em descrença e altas em eficácia profissional; que estudantes mais jovens e que realizam atividades de lazer apresentam maior eficácia profissional, diferentemente de estudantes das séries iniciais e que não realizam atividades extracurriculares; conciliar trabalho e estudos influenciou negativamente apenas o fator eficácia profissional, enquanto a intenção de desistir do curso influenciou negativamente os fatores descrença e eficácia profissional. CONCLUSÃO: faz-se necessário o reconhecimento das situações que levam os estudantes à exaustão emocional, considerando a especificidade de seus ambientes de formação. .

OBJETIVO: investigar la síndrome de burnout y su relación con variables sociodemográficas y académicas, entre estudiantes de pregrado en enfermería de una universidad pública del Sur de Brasil. MÉTODO: estudio cuantitativo, desarrollado con 168 estudiantes, mediante la aplicación de una adaptación del Maslach Burnout Inventory - Student Survey, validada para fines de ese estudio. Fueron utilizados los análisis descriptivo y de variancia para analizar los datos. RESULTADOS: se constató que los estudiantes no presentan la síndrome de burnout, manifestando altos promedios en Agotamiento Emocional, bajos en Descreencia y altos en Eficacia Profesional; que estudiantes más jóvenes y que practican actividades de ocio presentan mayor Eficacia Profesional, diferentemente de estudiantes de los años iniciales sin actividades extracurriculares; conciliar trabajo y estudios influyó negativamente apenas el factor Eficacia Profesional, mientras la intención de desistir del curso influyó negativamente los factores Descreencia y Eficacia Profesional. CONCLUSIÓN: es necesario reconocer las situaciones que llevan a los estudiantes al Agotamiento Emocional, considerando la especificidad de sus ambientes de formación. .

Rapid analysis of non-esterified fatty acids as methyl esters from different biological specimens by gas chromatography after one-step esterification.

A rapid gas chromatographic method for the determination of medium-chain and long-chain free fatty acids (C14:0 to C24:0 fatty acids) from different biological specimens is presented. After a rapid one-step transesterification method in methanol-acetyl chloride (50:1, v/v), fatty acid methyl esters were extracted into n-hexane and analysed on a 15-m Durabond-Wax column within a 12-min chromatographic run. The detection limit is 500 pg per injection.

Spin trapping of free radicals and lipid peroxidation in microsomal preparations from malignant hyperthermia susceptible pigs.

Microsomes were prepared from livers of malignant hyperthermia susceptible (MHS) or resistant (MHR) pigs. On incubation with the spin trap alpha-(4-pyridyl-l-oxide)-N-tert-butylnitrone (4-POBN), the microsomes from MHS pigs produced a characteristic electron spin resonance (ESR) signal at a greater rate than those from MHR pigs. Increased formation in the incubations of thiobarbituric acid reactive substances (TBARS) by the microsomes of the MHS pigs indicated an enhanced susceptibility to free radical-mediated lipid peroxidation. These results provide further evidence that MHS pigs have an antioxidant abnormality which may contribute to the fatal MH response. However the nature of the abnormality is unclear. The enhanced formation of unstable free radicals and indices of lipid peroxidation was not due to decreased vitamin E concentration or glutathione peroxidase activity in the microsomes. Furthermore, fatty acid profiles were similar in microsomes from MHS and MHR pigs indicating similar amounts of potential substrate for TBARS formation.

Detection of GTP-binding proteins in purified derivatives of rough endoplasmic reticulum.

As a first step in determining the molecular mechanism of membrane fusion stimulated by GTP in rough endoplasmic reticulum (RER), we have looked for GTP-binding proteins. Rough microsomes from rat liver were treated for the release of ribosomes, and the membrane proteins were separated by SDS/polyacrylamide-gel electrophoresis. The polypeptides were then blotted on to nitrocellulose sheets and incubated with [alpha-32P]GTP [Bhullar & Haslam (1987) Biochem. J. 245, 617-620]. A doublet of polypeptides (23 and 24 kDa) was detected in the presence of 2 microM-MgCl2. Binding of [alpha-32P]GTP was blocked by 1-5 mM-EDTA, 10-10,000 nM-GTP or 10 microM-GDP. Either guanosine 5'-[gamma-thio]triphosphate or guanosine 5'-[beta gamma-imido]triphosphate at 100 nM completely inhibited binding, but ATP, CTP or UTP at 10 mciroM did not. Pretreatment of microsomes by mild trypsin treatment (0.5-10 micrograms of trypsin/ml, concentrations known not to affect microsomal permeability) led to inhibition of [alpha-32P]GTP binding, suggesting a cytosolic membrane orientation for the GTP-binding proteins. Two-dimensional gel-electrophoretic analysis revealed the 23 and 24 kDa [alpha-32P]GTP-binding proteins to have similar acid isoelectric points. [alpha-32P]GTP binding occurred to similar proteins of rough microsomes from rat liver, rat prostate and dog pancreas, as well as to a 23 kDa protein of rough microsomes from frog liver, but occurred to distinctly different proteins in a rat liver plasma-membrane-enriched fraction. Thus [alpha-32P]GTP binding has been demonstrated to two low-molecular-mass (approx. 21 kDa) proteins in the rough endoplasmic reticulum of several varied cell types.

Heterogeneity of native rat liver elongation factor 2.

The high heterogeneity of native rat liver EF-2 prepared from either 105000 x g supernatant or microsome high-salt extract was detected by two-dimensional equilibrium isoelectric focusing-SDS-polyacrylamide gel electrophoresis in the presence of 9.5 M urea. Five spots were always detected, all of Mr 95,000, which were not artefactual for their amount varied when EF-2 was specifically ADP-ribosylated by diphtheria toxin in the presence of NAD+, and/or phosphorylated on a threonine residue by a Ca2+/calmodulin-dependent protein kinase (most likely Ca2+/calmodulin-dependent protein kinase III described by others [(1987) J. Biol. Chem. 262, 17299-17303; (1988) Nature 334, 170-173]). Results of ADP-ribosylation and/or phosphorylation experiments with either unlabeled or labeled reagents ([14C]NAD and [32P]ATP) strongly suggest that our preparation contained native ADP-ribosylated and native phosphorylated forms which could be estimated at about 20% and 40% of the whole EF-2. Phosphorylated and ADP-ribosylated forms of EF-2 could be ADP-ribosylated and phosphorylated, respectively, but a native form both ADP-ribosylated and phosphorylated was not detected. Our results also suggest the existence of a minor native form of EF-2 and of its phosphorylated and ADP-ribosylated derivatives.

Additional members of the rat liver lamin polypeptide family. Structural and immunological characterization.

In addition to lamins A, B, and C (Gerace, L., Blum, A., and Blobel, G. (1978) J. Cell Biol. 79, 546-566), the rat liver nuclear lamina has recently been shown to contain two higher molecular weight (70,000-75,000, pI 5.7-5.8) quantitatively less prominent nuclear polypeptides (Lehner, C.F., Kurer, V., Eppenberger, H. M., and Nigg, E. A. (1986) J. Biol. Chem. 261, 13293-13301). In the present study two-dimensional tryptic peptide mapping and Western blotting with affinity-purified chicken and human sera have been utilized to examine the structural relationships and the tissue distribution of these quantitatively less prominent mammalian lamins (termed lamins D and E in this study). Lamins D and E have indistinguishable one- and two-dimensional proteolytic maps. Whereas the one-dimensional proteolytic maps of lamins D and E show several degradation products which are of similar molecular mass to polypeptides seen in one-dimensional proteolytic maps of lamins A, B, and C, the two-dimensional tryptic maps of D and E are distinct from those of lamins A, B, and C, suggesting that lamins D and E are produced by transcription of one or more unique genes. Nonetheless, affinity-purified anti-D/E antibodies (raised against lamin E) cross-react with lamin B, suggesting the presence of a shared epitope. Moreover, a human autoantibody cross-reacts with all five lamins after affinity elution from any of the five, suggesting the presence of another epitope which is shared by all five polypeptides. All five lamins were undetectable in rodent epididymal sperm. In contrast, lamins D and E were readily detected in a variety of rat somatic tissues (liver, kidney, prostate, brain, heart) including lymphoid cells, a cell type depleted of lamins A and C. During mitogenic stimulation of lymphocytes, the signal for lamins A and C increased 5-fold, the signal for lamins D and E increased 2-fold, but the signal for lamin B remained unchanged, suggesting that levels of lamins D and E are regulated independently from those of the major lamins.

Oxygen reduction and lipid peroxidation by iron chelates with special reference to ferric nitrilotriacetate.

A certain iron chelate, ferric nitrilotriacetate (Fe3+-NTA) is nephrotoxic and also carcinogenic to the kidney in mice and rats, a distinguishing feature not shared by other iron chelates tested so far. Iron-promoted lipid peroxidation is thought to be responsible for the initial events. We examined its ability to initiate lipid peroxidation in vitro in comparison with that of other ferric chelates. Chelation of Fe2+ by nitrilotriacetate (NTA) enhanced the autoxidation of Fe2+. In the presence of Fe2+-NTA, lipid peroxidation occurred as measured by the formation of conjugated diene in detergent-dispersed linoleate micelles, and by the formation of thiobarbituric acid-reactive substances in the liposomes of rat liver microsomal lipids. Addition of ascorbic acid to Fe3+-NTA solution promoted dose-dependent consumption of dissolved oxygen, which indicates temporary reduction of iron. On reduction, Fe3+-NTA initiated lipid peroxidation both in the linoleate micelles and in the liposomes. Fe3+-NTA also initiated NADPH-dependent lipid peroxidation in rat liver microsomes. Although other chelators used (deferoxamine, EDTA, diethylenetriaminepentaacetic acid, ADP) enhanced autoxidation, reduction by ascorbic acid, or in vitro lipid peroxidation of linoleate micelles or liposomal lipids, NTA was the sole chelator that enhanced all the reactions.

Molecular basis for the sex-related difference in renal N-nitrosodimethylamine demethylase in C3H/HeJ mice.

Previous work with rat and rabbit liver enzymes has demonstrated that cytochrome P450IIE1 is responsible for the metabolism of N-nitrosodimethylamine (NDMA), a widely occurring carcinogen. The present study demonstrated that a similar enzyme also exists in the mouse kidney and is regulated by testosterone. These results can account for the reported sex-related difference in the renal metabolism of NDMA in mouse strains such as C3H/HeJ. NDMA demethylase activities (expressed as pmol/min/mg protein) in kidney microsomes of female and male C3H/HeJ mice were 3.0 +/- 0.7 and 51.9 +/- 11.2, respectively. After testosterone treatment (500 mg/kg b.w. in olive oil, s.c.) for 2 days, the renal NDMA demethylase activity of the female mice was elevated 17-fold. The difference and change in NDMA demethylase activity were accompanied by corresponding differences and changes in P450IIE1 as quantified by immunoblot analysis (using antibodies prepared against rat P450IIE1) as well as in the mRNA level for P450IIE1 as determined by Northern and slot blot analyses (using a cDNA probe containing the coding sequence of rat P450IIE1 gene). Based on gel electrophoresis, the molecular weight of mouse renal P450IIE1 was 52,000 and the size of mouse renal P450IIE1 mRNA was approximately 1.8 kilobases; both were similar to those found in rat liver and kidney. Renal P450IIE1 mRNA levels in female, male, and testosterone-treated female mice were at a ratio of 1:22:20. On the other hand, this testosterone-related difference was not observed in hepatic P450IIE1. In liver microsomes, there were no significant differences in NDMA demethylase activity, P450IIE1 content, and P450IIE1 mRNA level between male and female mice or between untreated and testosterone-treated female mice. The apparent Km value of NDMA demethylase in mouse kidney microsomes (22 to 27 microM NDMA) were similar to that in rat liver microsomes. Renal NDMA demethylase activity was inhibited by a monoclonal antibody prepared against rat P450IIE1. These results suggest that mouse renal P450IIE1 is similar to rat P450IIE1 and is responsible for the low Km form of NDMA demethylase activity. Nevertheless, only the mouse renal enzyme is regulated by testosterone.

rp-120: a common endogenous substrate for insulin and IGF-1 receptor-associated tyrosine kinase activity in the highly malignant AS-30D rat hepatoma cells.

Receptors for Insulin, Epidermal Growth Factor, Platelet-Derived Growth Factor and Insulin-like Growth Factor type 1 are tyrosine-specific protein kinases. This enzymatic activity may play a role in mediating the biological actions of these peptides. It has recently been identified a Mr 120 KDa glycoprotein in rat liver plasma membranes which can be phosphorylated by the insulin receptor and by the EGF receptor in a cell-free system and by the insulin receptor in intact cultured H-35 hepatoma cells. In the present report it is shown that the solubilized Insulin-like Growth Factor type 1 receptor can phosphorylate tyrosine residues in the same 120 KDa glycoprotein from the AS-30D rat hepatoma cells.

[The radioprotective action of long-term anoxia on the membrane lipids in irradiated turtles]. / Radioprotektornoe deistvie dlitel'noi anoksii na membrannye lipidy obluchennykh cherepakh.

It was shown that 80% of tortoises survived on day 45 after gamma irradiation (60Co, 4.2.10(2) Gy) in conditions of long-term (6 h) anoxia, against 5% survived after irradiation in normal conditions. It is suggested that the modifying effect of ionizing radiation under anoxic conditions is mainly associated with the decreased rate of peroxidation processes in membrane phospholipids and the enhanced radioresistance background during the first decade following irradiation.

Lipid peroxidation and physical properties of smooth and rough hepatoma microsomes.

Smooth and rough endoplasmic reticulum of two Morris hepatomas, the slow growing 9618A and the fast growing 3924A, have been isolated, and their biochemical composition, supramolecular organization, and response to the action of peroxidative agents have been studied. Cytochrome P450 content and lipid availability are the limiting factors of their peroxidizability. The hemoprotein content is reduced about 80% in hepatoma 9618A and is virtually absent in hepatoma 3924A. The peroxidizability decreases with increasing growth rate of the tumor. The protein, phospholipid, and cholesterol content, the fatty acid composition as well as the double bond index, and the saturated and unsaturated fatty acid content are reported. Differences have been found between normal liver and tumors and between the fractions within a given tumoral tissue. The molecular order, as determined by fluorescence anisotrophy decay of DPH, increases in total microsomes and in the smooth fraction going from liver 9618A to 3924A, whereas for the rough fraction it is the same in liver and hepatoma 9618A; in 3924A it increases of about 30%. Fluidity decreases in total microsomes going from liver to 3924A, to 9618A. In both the purified fractions it decreases with increasing deviation of the tumor.

Fatty acid composition of phospholipids in mitochondria and microsomes during diethylnitrosamine carcinogenesis in rat liver.

Changes in lipid composition and function of subcellular organelles have been described in transplanted and primary tumours. We examine here the fatty acid composition of individual phospholipids (PL) in hyperplastic nodules and primary hepatoma induced by diethylnitrosamine (DEN), compared to that of normal liver and of transplantable Yoshida AH-130 hepatoma. Phosphatidylcholine and phosphatidylethanolamine fatty acid composition in mitochondria and microsomes from primary hepatoma were markedly different from normal liver; C18:0/C18:1 ratio was lower and the ratio between monosaturated and polyunsaturated fatty acids was higher. Linoleic acid content of mitochondrial cardiolipin, usually very high in normal rat liver, was notably lower in primary hepatoma. Cholesterol/phospholipid ratio in both microsomes and mitochondria from DEN-induced hepatoma was higher than in normal liver. Hyperplastic nodules showed no changes in cholesterol content whereas modifications in fatty acid composition were already observable. These modifications of membrane structure may be related to the functional changes found in nodular cells. Changes in fatty acid composition of membrane phospholipids, occurring in both primary hepatoma and preneoplastic nodules, might be one of the causes for decreased rate of lipid peroxidation peculiar to these tissues.

The lipid composition of highly differentiated human hepatomas, with special reference to fatty acids.

The lipid compositions of homogenates and microsomal fractions derived from surgical samples of highly differentiated human hepatoma, morphologically normal regions outside the tumours and from normal livers were analysed. A few enzyme activities were also assayed. Hepatoma microsomes demonstrated considerably lowered levels of cytochromes P-450 and b5. Hepatoma homogenates exhibited increased levels of cholesterol, normal amounts of dolichyl-P and slightly lowered levels of total phospholipid. The levels of dolichol, dolichol ester and ubiquinone in hepatoma homogenates were prominently decreased. In tumour microsomes the levels of cholesterol and dolichyl phosphate were increased considerably while the levels of phospholipid and dolichol were lowered. The phospholipid composition of tumour homogenates was roughly similar to that of control tissue. In tumour microsomes the relative amounts of phosphatidylserine and phosphatidylinositol were about 30% decreased, whereas the major phospholipids showed minor increases in amount. The rate and pattern of incorporation of [3H]glycerol into individual phospholipids in liver slices from control and hepatoma tissue did not differ to any larger extent. The fatty acid composition of tumour homogenates exhibited minor differences in comparison to the control with the greatest changes in the sphingomyelin fraction. In hepatoma microsomes the fatty acid compositions of the major phospholipids were altered moderately, with evident decreases in the relative amounts of the long-chain polyunsaturated fatty acids. In hepatoma homogenates the fatty acid composition of dolichol esters differed only slightly from the control pattern. These results indicate that the major disturbance in the lipid metabolism of highly differentiated hepatomas is localized to the mevalonate pathway, thus affecting mainly the levels of cholesterol, dolichol and ubiquinone.

Cytidine 5'-triphosphate-dependent dolichol kinase and dolichol phosphatase activities and levels of dolichyl phosphate in microsomal fractions from highly differentiated human hepatomas.

Homogenates and microsomal fractions prepared from biopsies of highly differentiated human hepatocellular carcinomas were found to contain low levels of dolichol in comparison with control tissue. In contrast, the amount of dolichyl phosphate in tumor homogenates was unchanged and actually increased in the microsomal fraction. The pattern of individual polyisoprenoids, both in the free and the phosphorylated dolichol fractions of hepatomas, did not exhibit any major alterations compared to the control. The rates of incorporation of [3H]mevalonic acid into dolichol and dolichyl phosphate in hepatomas were low. The dolichol monophosphatase activities in microsomal fractions from hepatomas and controls did not show any major differences, whereas the activity of the CTP-dependent dolichol kinase was increased in tumor microsomes. Glycosylation of endogenous dolichyl phosphate and of total protein using certain nucleotide-activated sugars was found to be slightly elevated in microsomal fractions from the tumor itself when compared to the control. The reasons for the differences in the levels of polyisoprenoids in hepatomas and control tissue are discussed.

A high pressure liquid chromatographic method for the separation and quantitation of water-soluble radiolabeled benzene metabolites.

The glucuronide and sulfate conjugates of benzene metabolites as well as muconic acid and pre-phenyl- and phenylmercapturic acids were separated by ion-pairing HPLC. The HPLC method developed was suitable for automated analysis of a large number of tissue or excreta samples. p-Nitrophenyl [14C]glucuronide was used as an internal standard for quantitation of these water-soluble metabolites. Quantitation was verified by spiking liver tissue with various amounts of phenylsulfate or glucuronides of phenol, catechol, or hydroquinone and analyzing by HPLC. Values determined by HPLC analysis were within 10% of the actual amount with which the liver was spiked. The amount of metabolite present in urine following exposure to [3H]benzene was determined using p-nitrophenyl [14C]glucuronide as an internal standard. Phenylsulfate was the major water-soluble metabolite in the urine of F344 rats exposed to 50 ppm [3H]benzene for 6 h. Muconic acid and an unknown metabolite which decomposed in acidic media to phenylmercapturic acid were also present. Liver, however, contained a different metabolic profile. Phenylsulfate, muconic acid, and pre-phenylmercapturic acids as well as an unknown with a HPLC retention time of 7 min were the major metabolites in the liver. This indicates that urinary metabolite profiles may not be a true reflection of what is seen in individual tissues.

Presence of guanine nucleotide-binding proteins in a plant hypocotyl microsomal fraction.

The presence of specific guanine nucleotide-binding proteins in a zucchini (Cucurbita pepo L.) hypocotyl microsomal fraction was investigated. Polypeptides were separated by sodium dodecyl sulphate polyacrylamide gel electrophoresis and transferred to nitrocellulose. Incubation of nitrocellulose blots with [alpha-32P]GTP and [gamma-32P]GTP indicated the presence of four specific and distinct GTP-binding proteins with molecular masses of approx. 23.4 kDa, 24.8 kDa, 26.6 kDa and 28.5 kDa. Binding of [alpha-32P]GTP could be completely prevented by 30 microM GDP or 10 microM guanosine 5'[gamma-thio]triphosphate. This report presents evidence for the presence in a microsomal fraction from zucchini hypocotyls of Gn-proteins as defined by Bhullar and Haslam (1987) Biochem.J. 245, 617-620. The four plant proteins resemble animal Gn-proteins when molecular weights and GTP-binding specificities are considered.

[Content of cytochrome P-450 and its induction capacity in primary liver tumors in rats]. / Soderzhanie tsitokhroma P-450 i ego sposobnost' k induktsii v pervichnykh opukholiakh pecheni krys.

The content of cytochrome P-450 has been measured in primary hepatomas induced by diethylnitrosamine. As a rule, the enzyme content in hepatomas was decreased, as compared to normal liver and tumor-affected liver, but some hepatomas contained cytochrome P-450 in greater amount than normal tissue. Aroclor 1254 induced an increase in cytochrome P-450 content, which was identical in hepatomas, normal liver and tumor-affected liver. The dependence of hepatoma morphology on cytochrome P-450 content was not detected.

A membrane preparation that contains proteins characteristic of the rough endoplasmic reticulum.

We describe a procedure for disassembling rat liver rough microsomes, which allows the purification of the rough endoplasmic reticulum (ER) membrane. Membrane-bound ribosomes and adsorbed proteins are first detached by washing rough microsomes with 5 mM Na-pyrophosphate. In a second step, the vesicle membrane is opened by digitonin, with concomitant release of the luminal content. The purification is monitored at each step by electron microscopy, and by assaying chemical constituents (protein, phospholipid, RNA) and marker enzymes for the main subcellular organelles. The final membrane preparation is representative of the ER, since it contains 24.1% of the liver glucose 6-phosphatase with a relative specific activity of 14.2. Contaminants represent less than 5% of its protein content. SDS-polyacrylamide gel electrophoresis, followed by immunoblot analysis, reveals that the ribophorins I and II, two established markers of the rough (d) domain are still present in the final membrane preparation. It also contains the docking protein (or signal recognition particle receptor) and protein disulfide isomerase, and has conserved the functional capacity to remove co- and post-translationally the signal peptide of pre-secretory proteins. The membrane preparation is suitable for studies on the polypeptide composition of the d domain.

Hepatic metabolism and carcinogenesis. Its role in hepatoma and adenocarcinoma.

The effect of carcinogenesis on various hepatic microsomal parameters and related cell functions was studied in two tumor models. Hepatocarcinoma was produced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) (Solt-Farber model) and mammary adenocarcinoma using R3230 AC cancer cell line. In these models the effect of the tumor on metabolic functions of hepatocytes was studied. In the DEN/2AAF tumor model in nodules phase I components (cytochrome P-450, aminopyrine N-demethylase, arylhydrocarbon hydroxylase) were reduced, together with microsomal progesterone content and total and specific progesterone binding. Phase II components (glutathione, glutathione S-acyltransferase, UDP-glucuronyl transferase, epoxide hydrolase) were increased. In hepatoma the effects were more enhanced. Nodules grown in the speen retained the dedifferentiated enzyme characteristics. In the R3230 AC mammary adenocarcinoma phase I components of the hepatic endoplasmic reticulum were reduced, and phase II components increased. Progesterone content and receptor binding were also increased. These results indicate that enzymatic abnormalities in the liver cell are connected with cancer production and the hepatic dedifferentiation seems to be indistinguishable in tumor-bearing liver from those seen with extrahepatic neoplasms.

Effect of 7,8-benzoflavone pretreatment on diethylstilbestrol metabolism, drug-metabolising enzymes and the aromatic hydrocarbon (Ah) receptor in male hamster liver.

Pretreatment of male Syrian golden hamsters with 7,8-benzoflavone (7,8-BF) leads to a marked increase of cytochrome P450 and cytochrome b5 levels in the liver, whereas phenobarbital (PB) and 3-methylcholanthrene (MC) induce cytochrome P450 but not cytochrome b5 7,8-BF pretreatment has only minor effects on the activities of aryl hydrocarbon hydroxylase and 7-ethoxycoumarin-O-deethylase, but 7-ethoxyresorufin-O-deethylase is increased 3-fold. In contrast to PB, pretreatment with 7,8-BF or MC reduces the oxidative metabolism of diethylstilbestrol (DES) by hepatic microsomes in vitro. The cytosolic level of the aromatic hydrocarbon (Ah) receptor in hamster liver is decreased by 7,8-BF and slightly enhanced by MC pretreatment. PB increases the receptor level 1.5-fold. The affinity of 7,8-BF to the Ah receptor in vitro is of the same order of magnitude as that of the known ligands 5,6-benzoflavone and 2,3,7,8-tetrachlorodibenzofurane. PB and DES show no binding to the receptor protein.