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Biomedical subjects

A Seidel

Publications and source records attributed to A Seidel.

At least 163 records · Page 9Linked to original sources
PubMed1990

Rat liver endothelial and Kupffer cell-mediated mutagenicity of polycyclic aromatic hydrocarbons and aflatoxin B1.

The ability of isolated rat liver endothelial and Kupffer cells to activate benzo(a)pyrene (BP), trans-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (DDBP), trans-1,2-dihydroxy-1,2-dihydrochrysene (DDCH), and aflatoxin B1 (AFB1) to mutagenic metabolites was assessed by means of a cell-mediated bacterial mutagenicity assay and compared with the ability of parenchymal cells to activate these compounds. Endothelial and Kupffer cells from untreated rats were able to activate AFB1 and DDBP; DDBP was activated even in the absence of an NADPH-generating system. Pretreating the animals with Aroclor 1254 strongly enhanced the mutagenicity of the dihydrodiol, whereas the mutagenicity of AFB1 showed a slight increase. BP and DDCH were only activated by endothelial and Kupffer cells isolated from Aroclor 1254-pretreated rats. Parenchymal cells from untreated animals activated all four carcinogens tested; Aroclor 1254 enhanced the parenchymal cell-mediated mutagenicity of BP and DDCH but did not affect that of DDBP and clearly reduced that of AFB1. The reduced mutagenicity of AFB1 correlates with the decrease in the amount of 2 alpha-hydroxytestosterone formed when testosterone was incubated with parenchymal cell microsomes from Aroclor 1254-pretreated rats (compared with microsomes from untreated animals): the formation of 2 alpha-hydroxytestosterone is specifically catalyzed by cytochrome P-450h, a hemoprotein thought to be involved in the activation of AFB1. These results show that not only rat liver parenchymal cells, but also endothelial and Kupffer cells, activate several carcinogens to mutagenic metabolites.

Aflatoxin B1↗
PubMed1990

Stable expression of rat cytochrome P-450IA1 cDNA in V79 Chinese hamster cells and their use in mutagenicity testing.

V79 Chinese hamster cells genetically engineered to express cytochrome P-450IA1 are reported. A full length cDNA encoding rat cytochrome P-450IA1 was obtained from a cDNA library prepared from rat liver mRNA. The cDNA was recombined with the SV40 early promoter and expressed in V79 cells. Three V79-derived P-450IA1-expressing cell lines (XEM1, XEM2, and XEM3) were established. The presence of the rat cytochrome P-450IA1 cDNA in these hamster cells was confirmed by Southern blotting. The transcription of the cDNA into mRNA and translation into the desired cytochrome P-450 protein was detected by Northern and Western blotting. The enzymatic activity was determined by the cytochrome P-450IA1-dependent oxidation of benzo[a]pyrene and 7-ethoxycoumarin. After exposure to benzo[a]pyrene, the mutant frequency increased in XEM1 and XEM2 cells and was higher than in V79 cells in the presence of an exogenous activating system. The mutant frequency was even more increased when XEM1 and XEM2 cells were exposed to the proximate mutagen (trans)-7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene.

Animals↗
PubMed1990

Effects of adrenergic agonists and antagonists on the numbers of synaptic ribbons in the rat pineal gland.

In the pineal gland numbers of synaptic ribbons (SR) undergo day/night changes which parallel the rhythm of melatonin synthesis. Since pineal biosynthetic activity is controlled by activation of adrenoreceptors, we investigated the effects of adrenergic agonists and antagonists on pineal synaptic ribbon numbers and N-acetyltransferase (NAT) activity, the key enzyme of melatonin synthesis in rats. In vivo application of the beta-adrenergic antagonist propranolol decreased melatonin synthesis when given during the dark phase but did not affect SR numbers. Treatment during daytime with the beta-adrenergic agonist isoproterenol increased pineal NAT activity whereas SR numbers did not change. Norepinephrine stimulated NAT activity in vitro in a dose-dependent manner, but did not elevate SR numbers. Incubation with an analog of the second messenger cyclic adenosine monophosphate increased both NAT activity and SR numbers. These results suggest that the beta-adrenergic system does not play a decisive role in the regulation of the nocturnal increase in SR numbers observed in the rat pineal gland.

Animals↗
PubMed1989

Cellular aspects of retention and transport of inhaled soluble and insoluble actinide compounds in the rat lung.

The binding of 241Am-hydroxide polymers (as models for readily soluble actinide compounds) to the cell components of rat lung was investigated using differential centrifugation, density gradient centrifugation, gel chromatography, carrier-free electrophoresis and electron microscopic autoradiography (with 241Pu). Irregularly shaped and spherical mixed (U, Pu)O2 particles (as models for insoluble actinide compounds) were administered to rats by inhalation and intratracheal installation and the lung and organ retention was determined. Electron microscopic studies were performed with rat lung and with rat and bovine alveolar macrophages exposed to the actinide compounds in vitro. In the case of the mixed (U, Pu)O2 particles the lung retention was independent of the particle shape and route of administration. Whereas 241Am administered as a hydroxide polymer was transferred rapidly from lung to skeleton and liver, only a few percent of the initial alveolar deposit was found in these organs after mixed oxide inhalation. It is concluded that all types of particles are stored primarily within phagolysosomes of alveolar macrophages. In the case of readily soluble compounds, the actinides are solubilized within these lysosomes and become bound to cytosolic ferritin in the alveolar macrophages. They are then released from the macrophages and probably cross the alveolar membranes as transferrin or as low-molecular-weight forms. Insoluble compounds remain within the lysosomes of alveolar macrophages, but there are indications of chemical damage to the lysosomal membranes, causing the particles to lie free in the cytoplasm.

Actinoid Series Elements↗
PubMed1989

One millisecond of light suffices to suppress nighttime pineal melatonin synthesis in rats.

The effect of a single high-intensity light pulse with a duration of 1 ms on nighttime pineal activity of male Sprague-Dawley rats was investigated. 10 minutes after light exposure pineal N-actyltransferase activity and melatonin content were significantly reduced. These results show that the rat pineal is capable of responding to very short light flashes of high intensity.

Acetyltransferases↗
PubMed1989

Effects of electrical stimulation of the superior cervical ganglia on the number of "synaptic" ribbons and the activity of melatonin-forming enzymes in the rat pineal gland.

Melatonin metabolism in the mammalian pineal gland is under the clear influence of sympathetic fibers originating in the superior cervical ganglia (SCG). Previous studies suggested that pineal "synaptic" ribbons (SR) as well are regulated by the gland's sympathetic innervation. To gain more insight into the mechanisms involved, we examined the effects of sympathetic stimulation on SR number and on the activity of melatonin forming enzymes, serotonin N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). The SCG in adult male rats were stimulated electrically during daytime for either 15 or 120 min. Immediately following stimulation, the glands were removed and processed for electron microscopy and for the determination of NAT and HIOMT activities. No differences in pineal SR number, size or location were found in rats stimulated with either parameters when compared with sham-stimulated or control animals. While the activity of HIOMT remained unchanged, the activity of NAT was also unaltered following 15 min of stimulation, but was augmented approximately three-fold in animals stimulated for 120 min. It is concluded that if SR in the rat pineal gland are under sympathetic control, the regulation is different from that involved in melatonin formation.

Acetylserotonin O-Methyltransferase↗
PubMed1989

The in vitro effects of high-Tc-superconducting particles (YBa2Cu3O6-7) and quartz (SiO2) on bovine alveolar macrophages.

The cytotoxic effects of YBa2Cu3O6--7-particles on cultured bovine alveolar macrophages were investigated by monitoring the release of lactate dehydrogenase and N-acetylglucosaminidase into the culture medium and testing the viability of the cells. After 20 hours of incubation the effects of YBa2Cu3O6--7-particles were very similar to those of analogous mass concentrations of DQ 12 quartz.

Acetylglucosaminidase↗
PubMed1989

Behaviour of spherical and irregular (U,Pu)O2 particles after inhalation or intratracheal instillation in rat lung and during in vitro culture with bovine alveolar macrophages.

Spherical and irregularly shaped mixed (U,Pu) oxide particles were administered to rats by inhalation and by intratracheal instillation. The lung retention of the particles was independent of particle shape and of the route of administration. Only a small percentage of the administered radioactivity was found in other organs. Detailed electron microscopic studies showed particles within membrane-enclosed vacuoles as well as lying free in the cytoplasm.

Administration, Inhalation↗
PubMed1989

Development and validation of a radioimmunoassay for serum melatonin.

A radioimmunoassay using N-[3-(4-hydroxy-3-[4-hydroxy-3- [125I]iodophenylpropionyl)]-5-methoxytryptamine as tracer for determination of melatonin in the serum of different species is described. Melatonin antisera were raised in rabbits by immunization with a bovine serum albumin conjugate of N-[3-(2-aminoethyl)-5-methoxy indole] hemisuccinamide. A single high affinity, specific antiserum was obtained. In contrast to previous studies, the tracer was synthesised in one step in the absence of water, giving an excellent yield of highly pure product. No chromatographic purification step was needed. Polyethylene glycol in combination with goat antirabbit immunoglobulins was used to separate bound and unbound tracer. Sera were delipidized with Lipoclean prior the extraction of melatonin with diethyl ether. This sample preparation allows the determination of melatonin in the presence of widely varying amounts of lipids in human, rat and hamster serum. Using this extraction procedure, the sensitivity of the radioimmunoassay was approximately 1 ng/l of serum. Dilutions of sera and of synthetic melatonin gave the same parallel response in the radioimmunoassay. High performance liquid chromatography analysis of a serum extract showed only one immunoreactive peak co-eluting with synthetic melatonin. Characteristic diurnal rhythms of melatonin were observed in all species. All assay components including standards and serum controls are stable for at least 1 year at 4 degrees C, thus facilitating the determination of melatonin in a routine laboratory.

5-Methoxytryptamine↗
PubMed1989

Serotonin and melatonin contents in the pineal glands from different stocks and strains of laboratory rats.

In the present study the pineal gland was examined in 2 outbred stocks and 6 inbred strains of rats some of which were pigmented to varying degrees, to see whether inbreeding affects the variability and whether differences exist between albino and pigmented rats. The animals were kept under 12 h light: 12 h darkness (12 L:12 D) and killed 7 h after the onset of light and darkness, respectively. The parameters examined were pineal protein content, serotonin and melatonin levels and hydroxyindole-O-methyltransferase (HIOMT) activity. All the parameters examined revealed interstrain differences, independently of whether the data were expressed per pineal or per mg protein. The variation coefficients for the various parameters were relatively high. They were mostly smaller when the data were expressed per pineal rather than per mg protein. No striking differences existed between the variation coefficients in inbred and outbred rats. When pineal size and the melatonin-related parameters expressed per pineal were used to assess the melatonin-synthesizing capacity of the pineal glands, it was found that the outbred Wistar and Sprague-Dawley rats and the inbred LEWIS-derived (LEW/Han) rats, all of which were albinos, had the most active pineals. Intermediate activity was noted in the hooded E3/Han and BDE/Han and the albino BDII/Han rats. The smallest and least active pineals were found in the totally pigmented BN/Han and DA/Han rats. The results taken together show that different stocks and strains exhibit significant differences in pineal size and melatonin-forming capacity. Albino rats appear to have larger and more active pineals than pigmented rats.

Acetylserotonin O-Methyltransferase↗
PubMed1988

Microsomal metabolism of picene.

Picene, a polycyclic aromatic hydrocarbon (PAH) of environmental relevance has recently been predicted to be carcinogenic, based on quantum mechanical calculation, although in several animal studies no carcinogenicity could be detected. In order to find out if the metabolism of this PAH can provide an explanation for its lack of carcinogenicity, picene was incubated with the hepatic microsomal fraction of Sprague-Dawley rats, which had been pretreated with Aroclor 1254. Sixteen ethyl acetate-extractable metabolites could be separated by reversed-phase high-performance liquid chromatography. Comparison of the chromatographic behavior and the UV and mass spectral properties of the metabolites with those of synthetic derivatives of picene allowed the identification of trans-1,2-, -3,4-, -5,6-dihydrodiol as well as 2- and 4-phenol as microsomal metabolites of picene. At a substrate concentration of 2.7 microM and an amount of 68 micrograms microsomal protein per ml incubation volume, 4-picenol was the main microsomal metabolite with 32.2% of total metabolic conversion, followed by the 1,2-(bay-region)dihydrodiol with 16.7%, the 3,4-(M-region)dihydrodiol with 15.9%, 2-picenol with 9.1% and the 5,6-(K-region)dihydrodiol with 1.6%. In this respect the metabolism of picene is not significantly different from that of the carcinogenic PAH benzo[a]pyrene and dibenz[a,h]anthracene. The M-region dihydrodiols, potential precursors of electrophilically reactive dihydrodiol bay-region epoxides, are formed from all three PAHs at 11-16% of total metabolic conversion. From the 2.8- to 4.4-fold lower amounts of polar and water-soluble metabolites of picene as compared to dibenz[a,h]anthracene and benzo[a]pyrene it is deduced that dihydrodiol epoxides are generated from picene to a much smaller extent than from the two carcinogenic PAHs. The lacking carcinogenicity of picene could therefore result from the inability of microsomal enzymes to transform its M-region dihydrodiol to dihydrodiol bay-region epoxides in amounts necessary to initiate carcinogenesis.

Animals↗
PubMed1987

Seasonal changes in circulating levels of thyroid hormones are not dependent on the age in Djungarian hamsters Phodopus sungorus.

1. Plasma levels of total and free thyroxine (T4; FT4) and triiodothyronine (T3; FT3) were measured by radioimmunoassay in adult and senescent Djungarian hamsters at different times of the year. 2. Seasonal changes of both hormones were found in adult and senescent hamsters. 3. However, except for total thyroxine, the patterns were different in both groups of hamsters. 4. These results suggest, that in Djungarian hamsters age-related changes of thyroid function do not affect the secretory activity of the thyroid gland rather than the phase of the seasonal cycle.

Acclimatization↗
PubMed1987

Distribution of 239Pu in the skeleton of the tree shrew (Tupaia belangeri) between 15 and 50 months after injection.

The macroscopic and microscopic distribution of intramuscularly injected, essentially monomeric, 239Pu was studied in the skeleton of the adult tree shrew (Tupaia belangeri). Data for the period between 15 and 50 months after injection are presented and compared with the data from earlier time points. Between 83 and 500 days after injection the nuclide content and the wet weight of the skeleton decreased to a constant level at about 55 per cent of the maximum values. The microscopic distribution has been analysed in distal femora, proximal humerus, proximal tibia and lumbar vertebra over the whole observation time; additionally at some selected time points proximal femur, femur shaft, distal humerus and distal tibia were analysed. The initial endosteal surface activity ranged from 3.8 to 5.3 Bq/cm2 and decreased to a minimum at about 1000 days after injection and increased thereafter. A similar behaviour was found for the dose rate near bone surfaces which was initially about 0.075 Gy/day on endosteal surfaces. In the deep bone and the deep marrow the dose rate was negligible, about 0.008 Gy/day and 0.001 Gy/day, respectively. The average cumulative dose 1500 days after injection was about 67 Gy on the endosteum, six times greater than the cumulative dose calculated from the mean concentration of plutonium in the whole skeleton. All values are normalized to an injected activity of 37 kBq/kg body weight. The tupaia data are discussed in relation to the available data from monkeys, dogs and rats.

Animals↗
PubMed1987

Association of plutonium with lysosomal, lipofuscin-like granules in Chinese hamster hepatocytes: evidence from electron microscopic and biochemical studies with 241Pu and 239Pu.

This electron-microscopic-autoradiographic study was undertaken to identify the cell organelles, which bind plutonium in Chinese hamster hepatocytes at different times after injection. Female Chinese hamsters were injected intraperitoneally with 241Pu and sacrificed at time intervals of between 4 days and 35 weeks. The Chinese hamster was chosen as the experimental animal as it is a species in which there is virtually no elimination of plutonium from the liver. From the 4th day onwards beta-tracks were found over globular electron-dense structures, which were randomly distributed in the cytoplasm of the hepatocytes and strongly resembled lipofuscin bodies. Comparison of the results with those from biochemical experiments showed good agreement between the morphological and biochemical observations. At early times after injection 241Pu was also found in the hepatocyte nuclei. All the evidence suggests that in this species plutonium in hepatocytes becomes bound to lipofuscin-accumulating lysosomes, which cannot be excreted.

Animals↗
PubMed1987

Metabolic activation to a mutagen of 3-hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, a secondary metabolite of benzo[a]pyrene.

3-Hydroxy-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (3-OH-BP-7,8-diol) was isolated from arylsulfatase/beta-glucuronidase-treated bile of rats to which 3-hydroxybenzo[a]pyrene (3-OH-BP) has been administered. This triol was investigated for mutagenicity in Salmonella typhimurium (reversion to histidine prototrophy of strains TA 97, TA 98, TA 100 and TA 1537) and in V79 Chinese hamster cells (acquisition of resistance to 6-thioguanine). When no exogenous metabolizing system was added the triol was inactive, while 3-OH-BP showed weak mutagenic effects with all four bacterial strains. In the presence of NADPH-fortified postmitochondrial supernatant fraction (S9 mix) of liver homogenate from Aroclor 1254-treated rats, the mutagenicity of 3-OH-BP was potentiated, and the triol was activated to a mutagen(s). In the presence of S9 mix, the triol was 5-18 times more mutagenic than 3-OH-BP in strains TA 97, TA 100 and TA 1537, but both compounds showed similar mutagenic potencies with strain TA 98. These strain differences strongly suggest that the mutagenicity of 3-OH-BP in the S9 mix-mediated test was not exclusively due to metabolites of 3-OH-BP-7,8-diol. Trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP-7,8-diol), like the triol, showed mutagenic effects only in the presence of S9 mix. Strain TA 1537 was reverted by the triol but not by the diol. In the other bacterial strains the diol was more mutagenic than the triol, the difference in potency being largest in strain TA 100 (2.5- to 10-fold, depending on the experimental conditions). In V79 cells, the diol was a potent mutagen, while the triol showed only very weak mutagenic effects. However the triol was more cytotoxic than the diol. High cytotoxicity of the triol was observed even in the absence of S9 mix. The results of the present study demonstrate that metabolites of 3-OH-BP-7,8-diol are biologically-active derivatives of benzo[a]pyrene. Comparison of the mutagenic effectiveness in different bacterial strains also reveals that metabolites of 3-OH-BP-7,8-diol and of BP-7,8-diol substantially differ in the kind of genetic alterations they evoke.

Animals↗